Assessment of Vasodilation Function in Diabetic Patients via Skin Temperature Variation Signals / 医用生物力学

Objective A program-controlled flexible multi-point temperature measurement device was self developed for collection and analysis of skin temperature signals of diabetic patients and healthy subjects under resting and heating conditions so as to assess vasodilation function of the microcirculation, Methods With reference to the endothelial regulation spectrum of human body, wavelet analysis was performed on skin temperature signals, and the temperature fluctuation amplitudes in diabetic group and healthy control group were compared at different time periods after thermal stimulation. Results The temperature fluctuation amplitude in endothelial spectrum of diabetic group was smaller than that of healthy control group, and the decrease in skin temperature fluctuation after the power-off of thermal stimulation was remarkably smaller than that of control group, indicating that the response to thermal stimulation for diabetic patients was slower. Conclusions Vasodilation function can be quantitatively evaluated by using the fluctuation of skin temperature signals in endothelial spectrum band. Skin temperature monitoring is a potentially easy-implemented method for the health management and early diagnosis of microvascular diseases in diabetic patients.

Phosphorylated PKM2 regulates endothelium-dependent vasodilation in diabetes / 中南大学学报(医学版)

OBJECTIVES@#Endothelium-dependent vasodilation dysfunction is the pathological basis of diabetic macroangiopathy. The utilization and adaptation of endothelial cells to high glucose determine the functional status of endothelial cells. Glycolysis pathway is the major energy source for endothelial cells. Abnormal glycolysis plays an important role in endothelium-dependent vasodilation dysfunction induced by high glucose. Pyruvate kinase isozyme type M2 (PKM2) is one of key enzymes in glycolysis pathway, phosphorylation of PKM2 can reduce the activity of pyruvate kinase and affect the glycolysis process of glucose. TEPP-46 can stabilize PKM2 in its tetramer form, reducing its dimer formation and phosphorylation. Using TEPP-46 as a tool drug to inhibit PKM2 phosphorylation, this study aims to explore the impact and potential mechanism of phosphorylated PKM2 (p-PKM2) on endothelial dependent vasodilation function in high glucose, and to provide a theoretical basis for finding new intervention targets for diabetic macroangiopathy.@*METHODS@#The mice were divided into 3 groups: a wild-type (WT) group (a control group, C57BL/6 mice) and a db/db group (a diabetic group, db/db mice), which were treated with the sodium carboxymethyl cellulose solution (solvent) by gavage once a day, and a TEPP-46 group (a treatment group, db/db mice+TEPP-46), which was gavaged with TEPP-46 (30 mg/kg) and sodium carboxymethyl cellulose solution once a day. After 12 weeks of treatment, the levels of p-PKM2 and PKM2 protein in thoracic aortas, plasma nitric oxide (NO) level and endothelium-dependent vasodilation function of thoracic aortas were detected. High glucose (30 mmol/L) with or without TEPP-46 (10 μmol/L), mannitol incubating human umbilical vein endothelial cells (HUVECs) for 72 hours, respectively. The level of NO in supernatant, the content of NO in cells, and the levels of p-PKM2 and PKM2 protein were detected. Finally, the effect of TEPP-46 on endothelial nitric oxide synthase (eNOS) phosphorylation was detected at the cellular and animal levels.@*RESULTS@#Compared with the control group, the levels of p-PKM2 in thoracic aortas of the diabetic group increased (P<0.05). The responsiveness of thoracic aortas in the diabetic group to acetylcholine (ACh) was 47% lower than that in the control group (P<0.05), and that in TEPP-46 treatment group was 28% higher than that in the diabetic group (P<0.05), while there was no statistically significant difference in the responsiveness of thoracic aortas to sodium nitroprusside (SNP). Compared with the control group, the plasma NO level of mice decreased in the diabetic group, while compared with the diabetic group, the phosphorylation of PKM2 in thoracic aortas decreased and the plasma NO level increased in the TEPP-46 group (both P<0.05). High glucose instead of mannitol induced the increase of PKM2 phosphorylation in HUVECs and reduced the level of NO in supernatant (both P<0.05). HUVECs incubated with TEPP-46 and high glucose reversed the reduction of NO production and secretion induced by high glucose while inhibiting PKM2 phosphorylation (both P<0.05). At the cellular and animal levels, TEPP-46 reversed the decrease of eNOS (ser1177) phosphorylation induced by high glucose (both P<0.05).@*CONCLUSIONS@#p-PKM2 may be involved in the process of endothelium-dependent vasodilation dysfunction in Type 2 diabetes by inhibiting p-eNOS (ser1177)/NO pathway.

Acute effects of exercise with blood flow restriction on endothelial function in healthy young and older populations: a systematic review / Efeitos agudos do exercício com restrição do fluxo sanguíneo na função endotelial de jovens e idosos saudáveis: uma revisão sistemática

The objective of this review is to identify the acute effects of blood flow restriction (BFR) with vs without exercise on endothelial function in healthy individuals and the changes in endothelial function in young and older adults following different levels of exclusive BFR vs free flow. Systematic searches were performed in the following databases: PubMed, Web of Science, Scopus, and Cochrane Library, from inception to July 17, 2021. The studies included healthy individuals who underwent assessments of endothelial function before and after experimental protocols through endothelium-dependent flow-mediated dilatation. In total, 4890 studies were screened, and 6 studies of moderate-to-high methodological quality (Physiotherapy Evidence Database scores 6 ­ 10) including 82 subjects (aged 24 ­ 68 years) were eligible. Overall, flow-mediated dilatation increased in the non-cuffed arm immediately and 15 minutes after exercise, with no change in the cuffed arm (BFR of 60 ­ 80 mmHg). In protocols without exercise, cuff pressures of 25 ­ 30 mmHg applied for 30 minutes did not promote changes in the endothelial function, while those > 50 mmHg induced a dose-dependent attenuation of flow-mediated dilatation only in young individuals. A moderate level of BFR appears to have no effect on endothelial function after acute exercise. In non-exercise conditions, reductions in flow-mediated dilatation seem to result from increased retrograde shear provoked by cuff pressures ≥ 50 mmHg in young but not in older adults. An exercise-related increase in antegrade shear rate leads to a greater nitric oxide-mediated vasodilator response. However, BFR appears to attenuate this effect in young but not in older individuals. (AU)

O objetivo desta revisão foi identificar os efeitos agudos da restrição do fluxo sanguíneo (RFS) com vs. sem exercício na função endotelial de indivíduos saudáveis, bem como as alterações na função endotelial em jovens e idosos após diferentes níveis de RFS vs. fluxo livre. Pesquisas sistemáticas foram realizadas nas bases United States National Library of Medicine (PubMed), Web of Science, Scopus e Cochrane Library até 17 de julho de 2021. Os estudos incluíram indivíduos saudáveis que avaliaram a função endotelial antes e após protocolos experimentais, por meio da dilatação mediada por fluxo. Foi selecionado o total de 4.890 estudos, e foram elegíveis seis de moderada a alta qualidade metodológica (Physioterapy Evidence Database 6 ­ 10 pontos), incluindo 82 indivíduos (24 ­ 68 anos). No geral, a dilatação mediada por fluxo aumentou no braço sem manguito, imediatamente e 15 minutos após o exercício, sem alteração no braço com manguito (RFS de 60 ­ 80 mmHg). Em protocolos sem exercício, pressões do manguito de 25 ­ 30 mmHg aplicadas por 30 minutos não promoveram alterações na função endotelial, enquanto aquelas > 50 mmHg induziram uma atenuação dose-dependente da dilatação mediada por fluxo em indivíduos jovens. Um nível moderado de RFS parece não ter efeito na função endotelial após uma sessão de exercício. Em condições sem exercício, as reduções na dilatação mediada por fluxo parecem resultar do aumento do cisalhamento retrógrado provocado por pressões do manguito ≥ 50 mmHg em jovens, mas não em idosos. O aumento da taxa de cisalhamento anterógrado relacionada ao exercício leva a maior resposta vasodilatadora mediada pelo óxido nítrico. No entanto, a RFS parece atenuar esse efeito em jovens, mas não em . (AU)

Thoracic aortic reactivity in obese patients submitted to aerobic exercise / Reatividade da aorta torácica em pacientes obesos submetidos ao exercício aeróbico / Reactividad de la aorta torácica en pacientes obesos sometidos a ejercicio aeróbico

ABSTRACT Introduction: Aerobic exercise can improve the function of the cardiovascular circulatory system, reducing morbidity and mortality from cardiovascular disease by stimulating the production of endogenous self-protection. Activating potassium channels in vascular smooth muscle cells can cause vasodilation and increase blood flow, lowering blood pressure. There is a sensitivity to intracellular ATP and ADP concentration among the variety of potassium channels distributed in vascular smooth muscle cells, which vary mainly during aerobic physical activity. Objective: Explore the effect of aerobic exercise on the vascular reactivity of the thoracic aorta in patients with obesity and hyperlipidemia. Methods: Randomized controlled trial in twenty male Wistar rats weighing 250g and two months old. The control group remained at rest while the experimental group performed aerobic exercise on a treadmill at increasing speed for eight weeks. The rats were dissected, and dilatators and vasoconstrictors drugs stimulated their blood vessels in a tamponade solution. Observation of vascular changes was measured under controlled tensioning. Results: The blockade of KATP channels in vascular smooth muscle caused tonic contraction of vascular smooth muscle cells and increased blood pressure. Conclusion: Long-term regular aerobic exercise may induce changes in rats' thoracic aortic vascular function and vascular smooth muscle reactivity. Aerobic exercise can also significantly improve the activity of KATP channels. Evidence Level II; Therapeutic Studies - Investigating the results.

RESUMO Introdução: O exercício aeróbico pode melhorar a função do sistema circulatório cardiovascular, reduzindo a morbidade e mortalidade de doenças cardiovasculares estimulando a produção de autoproteções endógenas. A ativação de canais de potássio nas células musculares lisas vasculares pode causar vasodilatação e aumentar o fluxo sanguíneo, diminuindo a pressão sanguínea. Há uma sensível a concentração de ATP intracelular e ADP dentre a variedade de canais de potássio distribuídos em células musculares lisas vasculares, que variam principalmente durante a atividade física aeróbica. Objetivo: Explorar o efeito do exercício aeróbico na reatividade vascular da aorta torácica em pacientes com obesidade e hiperlipidemia. Métodos: Estudo randomizado controlado em vinte ratos Wistar machos de 250g e 2 meses de idade. O grupo controle permaneceu sob repouso enquanto o experimental realizava exercícios aeróbicos em esteira com velocidade crescente durante 8 semanas. Os ratos foram dissecados e seus vasos sanguíneos estimulados com drogas vasoconstritoras e dilatadoras em solução tampão. A observação das alterações vasculares foi mensurada sob tensionamento controlado. Resultados: O bloqueio dos canais KATP no músculo liso vascular causou contração tônica das células musculares lisas vasculares e aumento da pressão arterial. Conclusão: Exercícios aeróbicos regulares de longo prazo podem induzir alterações na função vascular da aorta torácica e reatividade do músculo liso vascular em ratos. O exercício aeróbico também pode melhorar significativamente a atividade dos canais KATP. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El ejercicio aeróbico puede mejorar la función del sistema circulatorio cardiovascular, reduciendo la morbilidad y la mortalidad de las enfermedades cardiovasculares al estimular la producción de autoprotección endógena. La activación de los canales de potasio en las células del músculo liso vascular puede causar vasodilatación y aumentar el flujo sanguíneo, reduciendo la presión arterial. Existe una sensibilidad a la concentración intracelular de ATP y ADP entre la variedad de canales de potasio distribuidos en las células del músculo liso vascular, que varían principalmente durante la actividad física aeróbica. Objetivo: Explorar el efecto del ejercicio aeróbico sobre la reactividad vascular de la aorta torácica en pacientes con obesidad e hiperlipidemia. Métodos: Ensayo controlado aleatorio en veinte ratas Wistar macho de 250 g y 2 meses de edad. El grupo de control permaneció en reposo mientras que el grupo experimental realizó ejercicios aeróbicos en una cinta de correr a velocidad creciente durante 8 semanas. Las ratas fueron disecadas y sus vasos sanguíneos fueron estimulados con fármacos vasoconstrictores y dilatadores en solución amortiguada. La observación de los cambios vasculares se midió bajo tensión controlada. Resultados: El bloqueo de los canales KATP en el músculo liso vascular provocó una contracción tónica de las células del músculo liso vascular y un aumento de la presión arterial. Conclusión: El ejercicio aeróbico regular a largo plazo puede inducir cambios en la función vascular de la aorta torácica y en la reactividad del músculo liso vascular en ratas. El ejercicio aeróbico también puede mejorar significativamente la actividad del canal KATP. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

Dependencia endotelial del efecto de canfenol plus 3 % sobre el músculo liso vascular arterial / Endothelial dependence of the effect of 3 % camphenol plus on arterial vascular smooth muscl

RESUMEN Introducción: el canfenol plus, es un derivado clorado del fenol empleado de forma habitual como medicación intraconducto durante los tratamientos pulporradiculares en Estomatología. Son escasos los estudios en relación con sus efectos sobre el músculo liso vascular arterial y la participación del endotelio en estos. Objetivo: determinar la dependencia endotelial del efecto de canfenol plus 3 % sobre el músculo liso vascular arterial. Material y Métodos: se realizó una investigación experimental preclínica utilizando 26 anillos de carótida externa desprovistos de endotelio vascular. Las preparaciones realizadas se colocaron en baño de órganos, registrándose la tensión desarrollada por el músculo liso vascular tras la adición de acetilcolina, así como de soluciones de canfenol plus 3 % durante diferentes intervalos de tiempo. La dependencia entre ambas tensiones, se determinó a través de un modelo de regresión lineal simple. Resultados: tras la preactivación con solución Krebs concentrada de iones potasio, la adición de 10 μl de acetilcolina y canfenol plus 3 %, indujeron una discreta, pero significativa vasorrelajación de la musculatura lisa vascular. El modelo de regresión lineal elaborado, demostró la dependencia entre las variables tensión producida por acetilcolina y tensión producida por el fármaco al décimo minuto, corroborando la implicación del endotelio vascular en dicho efecto relajante. Conclusiones: el canfenol plus 3 %, produjo in vitro, un efecto vasorrelajante sobre la musculatura lisa de anillos de carótida externa, dependiente de endotelio y a partir de un factor relajante o hiperpolarizante derivado de este.

ABSTRACT Introduction: Camphenol plus is a chlorinated phenol derivative commonly used as intracanal medication during pulporradicular treatments in Dentistry. Studies in relation to its effects on arterial vascular smooth muscle and the involvement of the endothelium in them are scarce. Objective: To determine the endothelial dependence of the effect of 3 % camphenol plus on arterial vascular smooth muscle. Material and Methods: A preclinical experimental research was carried out using 26 external carotid artery rings devoid of vascular endothelium. The preparations made were placed in an organ bath, recording the tension developed by the vascular smooth muscle after the addition of acetylcholine, as well as 3 % Camphenol plus solutions during different intervals of time. The dependence between both tensions was determined through a simple linear regression model. Results: After pre-activation with Krebs concentrated potassium ion solution, the addition of 10 μl of acetylcholine and 3 % camphenol plus induced a discrete but significant vasorelaxation of the vascular smooth muscle. The linear regression model developed demonstrated the dependence between the variables tension produced by acetylcholine and tension produced by the drug at the tenth minute, corroborating the involvement of the vascular endothelium in that vasorelaxant effect. Conclusions: It is concluded that 3 % Camphenol plus in vitro, produced a vasorelaxant effect on the smooth muscle of external carotid rings dependent on endothelium and from a relaxing or hiperpolarizing factor derived from it.

Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia / 中国结合医学杂志

OBJECTIVE@#To explore the effect of Kuanxiong Aerosol (KXA) on isoproterenol (ISO)-induced myocardial injury in rat models.@*METHODS@#Totally 24 rats were radomly divided into control, ISO, KXA low-dose and high-dose groups according to the randomized block design method, and were administered by intragastric administration for 10 consecutive days, and on the 9th and 10th days, rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA. In addition, the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test. The influence of KXA on the expression of calcium-CaM-dependent protein kinase II (CaMK II)/extracellular regulated protein kinases (ERK) signaling pathway has also been tested.@*RESULTS@#KXA significantly reduced the ISO-induced increase in ST-segment, interventricular septal thickness, cardiac mass index and cardiac tissue pathological changes in rats. Moreover, the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine (NE) or potassium chloride (KCl) was increased after KXA treatment in an endothelium-independent manner, and was attenuated by preincubation with verapamil, but not with tetraethylammonium chloride, 4-aminopyridine, glibenclamide, or barium chloride. KXA pretreatment attenuated vasoconstriction induced by CaCl2 in Ca2+-free solutions containing K+ or NE. In addition, KXA pretreatment inhibited accumulation of Ca2+ in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK II and p-ERK levels.@*CONCLUSION@#KXA may inhibit influx and release of calcium and activate the CaMK II/ERK signaling pathway to produce vasodilatory effects, thereby improving myocardial injury.

Efecto del 4-Clorofenol sobre el músculo liso vascular de aorta abdominal de ratas Wistar / Effect of 4-Chlorophenol on the vascular smooth muscle of the abdominal aorta of Wistar rats

Introducción: Uno de los derivados de los clorofenoles más utilizado en Estomatología, lo constituye el p-clorofenol (4-clorofenol), empleado como agente antibacteriano en la desinfección del conducto radicular durante el tratamiento pulporradicular. Son escasos los reportes científicos sobre sus efectos en la musculatura lisa vascular arterial y la regulación del flujo sanguíneo local. Objetivo: Determinar el efecto del 4-clorofenol sobre el músculo liso vascular de aorta abdominal de ratas Wistar. Material y Métodos: Se realizó una investigación experimental preclínica, utilizando 30 anillos de aorta abdominal (porción superior) obtenidos de ratas Wistar adultas. Las preparaciones de unos 5 mm se colocaron en baño de órganos, registrándose la tensión desarrollada por el músculo liso vascular tras la adición de 4-clorofenol en diferentes concentraciones y durante diferentes intervalos de tiempo. Resultados: El 4-clorofenol, tras la preactivación del musculo liso vascular de anillos de aorta abdominal, indujo relajación del vaso, la que se incrementó durante todo el tiempo de estudio y al aumento de la concentración del medicamento. Existieron diferencias significativas entre los valores de tensión promedios registrados en los diferentes intervalos de tiempo con los de la tensión base inicial. Conclusiones: El p-clorofenol indujo in vitro, relajación del músculo liso vascular de aorta abdominal de ratas Wistar(AU)

Introduction: In Dentistry, p-chlorophenol (4-chlorophenol) is one of the most widely used derivatives of chlorophenols. It is used as an antibacterial agent in root canal disinfection during pulp-radicular treatment. There are few scientific reports on its effects on vascular smooth musculature and the regulation of local blood flow. Objective: To determine the effect of 4-chlorophenol on vascular smooth muscle of abdominal aorta from Wistar rats. Material and Methods: A preclinical experimental research was carried out using 30 abdominal aortic rings (upper portion) obtained from adult Wistar rats. The preparations of about 5 mm were placed in an organ bath, recording the tension developed by the vascular smooth muscle after the addition of 4-chlorophenol at different concentrations and during different time intervals. Results: The results demonstrate that 4-Chlorophenol induced vasorelaxation after the preactivation of the vascular smooth muscle of the abdominal aortic rings, which increased during the entire study time and with increased drug concentration. There were significant differences among average tension values registered at different intervals of time in relation to the initial base tension. Conclusions: It is concluded that in vitro, p-chlorophenol induced relaxation of abdominal aorta vascular smooth muscle in Wistar rats(AU)

Efecto del Camphenol Plus sobre el músculo liso vascular de vena porta en ratas Wistar / Effect of Camphenol Plus on portal vein vascular smooth muscle in Wistar rats

RESUMEN Introducción: uno de los antisépticos comúnmente empleado en Estomatología desde el pasado siglo y que mantiene su uso hasta la actualidad, lo constituye el Camphenol Plus. Son escasos los reportes científicos de su efecto sobre el endotelio y la dinámica contráctil del músculo liso vascular, en especial de tejidos venosos como la vena porta hepática. Objetivo: determinar el efecto del Camphenol Plus sobre el músculo liso vascular de la vena porta. Métodos: se realizó una investigación experimental preclínica, con la utilización de 21 venas porta obtenidas de ratas Wistar. Las preparaciones realizadas se colocaron en baño de órganos, se registró la tensión desarrollada por el músculo liso vascular tras la adición de diez microlitros de Camphenol Plus, en diferentes concentraciones y durante diferentes intervalos de tiempo. Resultados: el Camphenol Plus, tras la preactivación del musculo liso vascular de la vena porta, indujo vasorelajación, la que se incrementó durante todo el tiempo de estudio y según el incremento de las concentraciones del medicamento. Existieron diferencias significativas entre los valores de tensión promedios registrados en los diferentes intervalos de tiempo con los de la tensión espontánea basal y la tensión base inicial. Conclusiones: el Camphenol Plus, indujo "in vitro", relajación de la musculatura lisa de la vena porta a través de un acoplamiento excitación-contracción de tipo farmacomecánico.

ABSTRACT Introduction: Camphenol Plus is one of the antiseptics commonly used in Dentistry since the last century and still in use today. There are few scientific reports of its effect on the endothelium and contractile dynamics of vascular smooth muscle, especially in venous tissues such as the hepatic portal vein. Objective: to determine the effect of Camphenol Plus on the vascular smooth muscle of the portal vein. Methods: a preclinical experimental investigation was carried out using 21 portal veins obtained from Wistar rats. The preparations were placed in an organ bath and the tension developed by the vascular smooth muscle was recorded after the addition of ten microliter of Camphenol Plus, at different concentrations and during different time intervals. Results: Camphenol Plus, after the preactivation of the vascular smooth muscle of the portal vein, induced relaxation, which increased throughout the study time and according to the increase in drug concentrations. There were significant differences between the average tension values recorded in the different time intervals with those of the basal spontaneous tension and the initial baseline tension. Conclusions: Camphenol Plus induced "in vitro" relaxation of portal venous smooth muscles through a pharmacomechanical excitation-contraction coupling.

Proteolytic activity of Triatoma infestans saliva associated with PAR-2 activation and vasodilation

Triatoma infestans (Hemiptera: Reduviidae) is a hematophagous insect and the main vector of Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae). In the present study, the authors investigated whether a serine protease activity from the saliva of T. infestans has a role in vasomotor modulation, and in the insect-blood feeding by cleaving and activating protease-activated receptors (PARs). Methods T. infestans saliva was chromatographed as previously reported for purification of triapsin, a serine protease. The cleavage activity of triapsin on PAR peptides was investigated based on FRET technology. Mass spectrometry was used to analyze the sites of PAR-2 peptide cleaved by triapsin. NO measurements were performed using the DAN assay (2,3-diaminonapthalene). The vasorelaxant activity of triapsin was measured in vessels with or without functional endothelium pre-contracted with phenylephrine (3 µM). Intravital microscopy was used to assess the effect of triapsin on mouse skin microcirculation. Results Triapsin was able to induce hydrolysis of PAR peptides and showed a higher preference for cleavage of the PAR-2 peptide. Analysis by mass spectrometry confirmed a single cleavage site, which corresponds to the activation site of the PAR-2 receptor. Triapsin induced dose-dependent NO release in cultured human umbilical vein endothelial cells (HUVECs), reaching a maximum effect at 17.58 nM. Triapsin purified by gel-filtration chromatography (10-16 to 10-9 M) was applied cumulatively to mouse mesenteric artery rings and showed a potent endothelium-dependent vasodilator effect (EC30 = 10-12 M). Nitric oxide seems to be partially responsible for this vasodilator effect because L-NAME (L-NG-nitroarginine methyl ester 300 µM), a nitric oxide synthetase inhibitor, did not abrogate the vasodilation activated by triapsin. Anti-PAR-2 antibody completely inhibited vasodilation observed in the presence of triapsin activity. Triapsin activity also induced an increase in the mouse ear venular diameter. Conclusion Data from this study suggest a plausible association between triapsin activity mediated PAR-2 activation and vasodilation caused by T. infestans saliva.(AU)

Effect of hyperuricemia treatment on vascular endothelial function in patients with cerebral infarction / 中华急诊医学杂志

Objective:To investigate the effect of hyperuricemia treatment on vascular endothelial function and blood pressure in patients with acute cerebral infarction.Methods:A total of 138 cases from the same center were enrolled in the study. 92 cases of acute cerebral infarction patients combined with hyperuricemia were selected. They were randomly divided into the experimental group (46 cases) and control group (46 cases). 46 cases of acute cerebral infarction patients with normal uric acid were selected in the same period. Patients in the experimental group received oral allopurinol for 3 months to treat hyperuricemia. Serum uric acid, blood lipid, and hs-CRP were tested before and after treatment in these populations. Blood pressure and body mass index (BMI) were also detected, and vascular endothelial function was evaluated using ultrasound non-invasive blood flow mediated vasodilation function (FMD). Comparison and statistical analysis were carried out in groups.Results:Uric acid [(479.7±49.0) μmol/L vs. (381.2±76.7) μmol/L]、hs-CRP[(8.1±6.7) mg/L vs. (5.1±4.6) mg/L]、systolic blood pressure [(124.7±26.3) mmHg vs. (97.4±13.5) mmHg] decreased significantly in the experimental group after 3 months of treatment with allopurinol ( P<0.05), and blood flow mediated vasodilation function [(7.6±3.5) vs. (11.2±3.9)]significantly increased ( P<0.05). The decrease of serum uric acid was positively correlated with the increase of FMD in the experimental group ( r=0.463, P<0.01). Multiple Regression analysis showed that serum uric acid was an independent predictor of FMD( β=-0.229, P=0.035). Conclusions:The treatment of hyperuricemia in patients with acute cerebral infarction can significantly improve the vascular endothelial function of patients, improve inflammation state and lower blood pressure. It is further confirmed that a higher uric acid level is related to worse endothelial function which may contribute to atherosclerosis.

Effect of Sanhuang Xiexintang in Inhibiting 7-Ketocholesterol-induced Endothelial Disfunctional by NIRP3 Inflammasome Pathway / 中国实验方剂学杂志

<b>Objective::To study whether Sanhuang Xiexintang (SHXXT) can restore endothelial function by inhibiting the activation of NOD-like receptor protein 3 (NIRP3) induced by 7-ketocholesterol (7-keto) in vascular endothelial cells. <b>Method::The aortic rings of mice were cultured in normal group, model (7-keto) group, SHXXT groups (1%, 2% and 5% drug-containing serum). Vasodilation function of mice was observed. Microvascular endothelial cells were cultured according to the above experimental groups, and NIRP3 inhibitor isoglycyrrhizin (ISO) group, was also set. Western blot was used to detect the expressions of endothelial nitric oxide synthase (eNOS), NIRP3, cysteinyl aspartate specific proteinase-1 (Caspase-1), interleukin-1<italic>β</italic> (IL-1<italic>β</italic>) protein. In addition, nitric oxide (NO) quantitative kit was used to detect the concentration of NO. <b>Result::Compared with the normal group, the endothelium-dependent vasodilation function of vascular rings was significantly reduced in model group (<italic>P</italic><0.01), and the drug group significantly restored the endothelium-dependent vasodilation function in a concentration-dependent manner (<italic>P</italic><0.05, <italic>P</italic><0.01). Meanwhile, microvascular endothelial cells were also studied. Compared with the normal group, the content of eNOS protein in the model group decreased (<italic>P</italic><0.05), while the concentration of NO decreased significantly (<italic>P</italic><0.01). After treatment with SHXXT serum, eNOS and NO could be restored, with significant differences in the concentration of NO with 5% (<italic>P</italic><0.05) and 10% (<italic>P</italic><0.01) SHXXT serum. At the same time, the expressions of NIRP3 (<italic>P</italic><0.05), cle-Caspase-1 activation (<italic>P</italic><0.01) and IL-1<italic>β</italic> production (<italic>P</italic><0.01) in endothelium were significantly increased under 7-keto stimulation, and the SHXXT serum could significantly inhibit the expression and activation of relevant proteins. Subsequently, endothelial cells were treated with NIRP3 inhibitor ISO. Compared with the model group, eNOS expression increased, and NO concentration increased significantly (<italic>P</italic><0.01) after treatment with ISO, but ISO had no synergistic effect on SHXXT serum. <b>Conclusion::SHXXT can improve endothelium-dependent vascular dysfunction induced by 7-keto, which is achieved by NO signaling pathway mediated by inhibiting the activation of endothelial NIRP3-related proteins.

Impact of gestational diabetes mellitus on vascular endothelial function in pregnant women / 中国医学影像技术

Objective: To explore the impact of gestational diabetes mellitus (GDM) on vascular endothelial function in pregnant women with endothelium-dependent flow-mediated dilatation (FMD) technology, and to observe the clinical value of FMD. Methods: Totally 29 pregnant women with GDM (observation group) and 34 normal pregnant women (control group) were collected. Endothelium-dependent FMD technology was used to obtain the right brachial artery FMD value before pregnancy, on the metaphase of pregnancy and 12 weeks postpartum. Clinical data, including pregnant women's age, heart rate, body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride and oral glucose tolerance test (OGTT) results were recorded and compared between 2 groups. FMD values were analyzed between groups and within group at different time points, and the impact factors of FMD values were explored. Results: FMD values showed first downward and then rising trend in both 2groups. Statistical differences of FMD values were found between observation group (F=85.50) and control group (F=89.59) at all 3 time points (all P0.05), while FMD of metaphase pregnancy (F=16.88) and 12 weeks postpartum (F=60.83) in control group were both larger than in observation group (both P<0.05).Blood glucose 2 hours after taking sugar and diastolic blood pressure had obvious impact on FMD value. Conclusion: GDM may lead to irreversible vascular endothelial dysfunction in pregnant women. Using FMD technology can noninvasively evaluate vascular endothelial function of GDM, which is expected to provide a new way for screening postpartum cardiovascular and cerebrovascular diseases in GDM pregnant women.

Efficacy and Safety of Modified Chaihu Jia Longgu Muli Tang in Treating Mild to Moderate Essential Hypertension Complicated with Depression and Liver-Yang Hyperactivity Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy and safety of modified Chaihu Jia Longgu Muli Tang in treating mild to moderate essential hypertension complicated with depression and liver-Yang hyperactivity syndrome.Method:Totally 121 mild to moderate hypertensive patients complicated with depression in line with the inclusive criteria were randomized into treatment group and control group. All of the enrolled patients in treatment group and control group were treated with conventional therapy. In treatment group, patients were given modified Chaihu Jia Longgu Muli Tang, one dose per day. The treatment course lasted for 4 weeks. Blood pressure, patient health questionnaire-9 (PHQ-9) score, score of traditional Chinese medicine syndrome, C-reactive protein (CRP), endothelial-dependent vasodilation, and adverse effect were observed in this study.Result:Both systolic blood pressure and diastolic blood pressure were significantly lowered when compared to control group (P<0.05). PHQ-9 score was significantly improved in treatment group (P<0.05). The score of traditional Chinese medicine syndrome was significantly improved in treatment group compared to control group (P<0.05). CRP was significantly improved in treatment group compared with control group (P<0.05). Endothelial-dependent vasodilation was significantly improved in treatment group compared with control group (P<0.05). No severe adverse effect was observed in this research.Conclusion:Chaihu Jia Longgu Muli Tang has a creation clinical efficacy in the treatment of mild to moderate essential hypertension with depression. In addition to the effect in reducing both systolic and diastolic blood pressure, modified Chaihu Jia Longgu Muli Tang was also effective in improving depression, traditional Chinese medicine syndrome and endothelial-dependent vasodilation, and reducing the level of CRP with little adverse effect.

Advances in pharmacological effects of higenamine on cardiovascular system / 药学学报

Higenamine (HG) is an active cardiotonic component isolated from Aconite. Chinese and foreign scholars have done a lot of research on the metabolism and pharmacological effects of HG, which confirmed that it has cardiovascular pharmacological effects of cardiactonic action and vasodilation for the treatment of heart failure and bradycardia, anti-oxidative and anti-apoptotic effects which can be used to protect the heart and reduce heart ischemia and reperfusion injury. In addition, HG inhibits the expression of iNOS mRNA by inhibiting the activity of the transcription factor NF-κB, inhibits the lipopolysaccharide (LPS)-induced NO product, and inhibits platelet aggregation and thrombus formation, thereby improving the experimental septic shock in animals. This article reviews the recent progress in cardiovasular pharmacology of HG, which will contribute to the further development and clinical application of it in the future.

L-arginine supplementation improves post-exercise hypotension in elderly women / Suplementação de l-arginina potencializa a hipotensão pós-exercício em mulheres idosas / La suplementación de l-arginina potencializa la hipotensión post ejercicio en mujeres de la tercera edad

ABSTRACT Introduction: L-Arginine supplementation increases plasma levels of nitric oxide (NO) metabolites, an important mediator of peripheral dilatation. Therefore, L-Arginine supplementation can improve the duration and magnitude of post-exercise hypotension. Objectives: This study investigated the effects of L-Arginine supplementation on post-exercise hypotension, femoral artery area and heart rate variability in elderly women. Methods: Twenty prehypertensive and hypertensive adult female participants were divided (in a random and balanced manner) into two groups (placebo and L-arginine). The participants ingested eight grams of inert substance (placebo group) or eight grams of L-Arginine (L-arginine group), dissolved in water, 90 min prior to the experimental session. The experimental session consisted of an isokinetic maximal strength test. Blood pressure was measured using an oscillometric device (Omron MX3 Plus, Bannockburn, US) every 10 minutes for 60 minutes after the experimental session. Femoral artery area (ultrasound) and heart rate variability were also analyzed. Data underwent repeated measures (ANOVA) analysis and respective assumptions. Results: L-Arginine supplementation associated with exercise produced a significant decrease in systolic blood pressure [placebo vs L-Arginine] (p <0.05) at the "half-life" time point (90 minutes after supplementation) (141±12 vs 130±11 mmHg) and 40 min. (146±13 vs 127±13 mmHg), 50 min. (145±20 vs 127±15 mmHg) and 60 min. (147±19 vs 129±14mmHg) post-exercise. No significant differences were identified in femoral artery area and heart rate variability. Conclusion: Acute L-Arginine supplementation can increase post-exercise hypotension effects in elderly women. Additionally, acute L-Arginine supplementation is not related to either femoral artery area or heart rate variability responses. Level of evidence I; Randomized clinical trial.

RESUMO Introdução: A suplementação de L-arginina aumenta os níveis plasmáticos dos metabólitos de óxido nítrico, um importante mediador da dilatação periférica. Dessa forma, é possível que a suplementação de L-arginina maximize a duração e a magnitude dos efeitos hipotensores pós-exercício. Objetivos: O presente estudo investigou os efeitos da suplementação de L-arginina na hipotensão pós-exercício, área da artéria femoral e variabilidade da frequência cardíaca em mulheres idosas. Métodos: Vinte participantes, adultas, pré-hipertensas e hipertensas foram divididas (de modo aleatório e equilibrado)em dois grupos (placebo e L-arginina). As participantes ingeriram oito gramas de substância inerte (grupo placebo) ou oito gramas de L-arginina (grupo L-arginina), dissolvido em água, 90 min antes da realização da sessão experimental. A sessão experimental consistia em um teste de força isocinética máxima. A pressão arterial foi aferida utilizando um dispositivo oscilométrico (Omron MX3 Plus, Bannockburn, EUA) a cada 10 minutos, durante 60 minutos, após o término da sessão experimental. Foram analisadas ainda a variabilidade da frequência cardíaca e a área da artéria femoral (ultrassom). Os dados foram submetidos à análise de variância para medidas repetidas (ANOVA) e seus respectivos pressupostos. Resultados: A suplementação de L-arginina associada ao exercício promoveu redução significativa da pressão arterial sistólica [placebo vs. L-arginina] (p<0,05) no intervalo de "meia-vida" (90 minutos após a suplementação) (141±12 vs. 130±11 mmHg) e aos 40 min. (146±13 vs. 127±13 mmHg), 50 min. (145±20 vs. 127±15 mmHg) e 60 min. (147±19 vs. 129±14 mmHg) pós-exercício. Não foram identificadas diferenças significativas na área da artéria femoral e na variabilidade da frequência cardíaca. Conclusão: A suplementação aguda de L-arginina pode potencializar os efeitos hipotensores pós-exercício em mulheres idosas. Além disso, a suplementação de L-arginina aguda não está associada às respostas de variabilidade da frequência cardíaca ou da área da artéria femoral. Nível de evidência I; Ensaio clínico randomizado.

RESUMEN Introducción: La suplementación de L-arginina aumenta los niveles plasmáticos de los metabolitos de óxido nítrico, un importante mediador de la dilatación periférica. De esa forma, es posible que la suplementación de L-arginina maximice la duración y la magnitud de los efectos hipotensores post ejercicio. Objetivos: El presente estudio investigó los efectos de la suplementación de L-arginina en la hipotensión post ejercicio, área de la arteria femoral y variabilidad de la frecuencia cardíaca en mujeres de la tercera edad. Métodos: Veinte participantes, adultas, pre hipertensas e hipertensas fueron divididas (de modo aleatorio y equilibrado) en dos grupos (placebo y L-arginina). Las participantes ingirieron ocho gramos de sustancia inerte (grupo placebo) u ocho gramos de L-arginina (grupo L-arginina), disuelta en agua, 90 minutos antes de la realización de la sesión experimental. La sesión experimental consistía en un test de fuerza isocinética máxima. La presión arterial fue medida utilizando un dispositivo oscilométrico (Omron MX3 Plus, Bannockburn, EE.UU.) a cada 10 minutos, durante 60 minutos, después del término de la sesión experimental. Fueron analizadas además la variabilidad de la frecuencia cardíaca y el área de la arteria femoral (ultrasonido). Los datos fueron sometidos a análisis de variancia para medidas repetidas (ANOVA) y sus respectivas premisas. Resultados: La suplementación de L-arginina asociada al ejercicio promovió reducción significativa de la presión arterial sistólica [placebo vs. L-arginina] (p<0,05) en el intervalo de "media vida" (90 minutos después de la suplementación) (141±12 vs. 130±11 mmHg) y a los 40 min. (146±13 vs. 127±13 mmHg), 50 min. (145±20 vs. 127±15 mmHg) y 60 min. (147±19 vs. 129±14 mmHg) post ejercicio. No fueron identificadas diferencias significativas en el área de la arteria femoral ni en la variabilidad de la frecuencia cardíaca. Conclusión: La suplementación aguda de L-arginina puede potencializar los efectos hipotensores post ejercicio en mujeres de la tercera edad. Además, la suplementación de L-arginina aguda no está asociada a las respuestas de variabilidad de la frecuencia cardíaca o del área de la arteria femoral. Nivel de evidencia I; Ensayo clínico aleatorizado.

Effects of Isometric Handgrip Exercise versus Aerobic Exercise on Arterial Stiffness and Brachial Artery Flow-Mediated Dilation in Older Hypertensive Patients / 대한스포츠의학회지

PURPOSE: Isometric handgrip exercise (IHE) is an easy and accessible form of exercise that has beneficial effects on blood pressure (BP). However, it remains unclear whether IHE is similar benefits on arterial stiffness and endothelial function compared with aerobic exercise (AE) in elderly hypertensive patients. The aim of this study was to compare the effects of IHE versus AE on arterial stiffness and endothelial function in elderly hypertensive patients.METHODS: We conducted a randomized controlled trial with a three-arm design. Fifty-four elderly hypertensive patients (15 men; mean age, 69±6 years; systolic blood pressure, 131.2±14.7; diastolic blood pressure, 80.2±7.9 mm Hg) were randomized to IHE training (n=18), AE training (n=21), or non-exercise control group (n=21) for 12 weeks. Bilateral IHE training was performed four times of 2 minutes at 30% of maximal voluntary contraction with three times per week. AE training was performed brisk walking for 30 minutes at moderate intensity with three times per week. Carotid-femoral pulse wave velocity (PWV), augmentation index heart rate corrected (AIx@75 bpm) and brachial artery flow-mediated vasodilation (FMD) as indices of arterial stiffness and endothelial function were measured at baseline and after the intervention.RESULTS: Following 12-week intervention, resting BP was significantly decreased in both IHE (p=0.001) and AE groups (p=0.002). AIx@75 bpm and FMD were unchanged in the all groups. However, PWV was significantly decreased in both IHE and AE groups (IHE, 10.9±2.3 to 9.9±2.1 m/s [p<0.001]; AE, 10.5±2.0 to 9.4±1.6 m/s [p=0.001]), without any change in the control group.CONCLUSION: These findings suggest that both IHE and AE trainings were comparable effect in improving arterial stiffness in elderly hypertensive patients.

Power Doppler ultrasound-guided sialography using the phenomenon of increased blood flow: A technical report

PURPOSE: This report presents a procedure for performing power Doppler ultrasound-guided sialography using the phenomenon of increased blood flow and illustrates its application to practical patient cases.MATERIALS AND METHODS: The salivary gland was scanned using ultrasound equipment (GE LOGIQ5 Expert® device; GE Medical Systems, Milwaukee, WI, USA) to identify pathological findings related to the patient's chief complaint. To identify the orifice of the main duct, it should be cannulated using a lacrimal dilator. After inserting the catheter into the cannulated main duct, the position of the catheter within the duct was confirmed by ultrasound. A contrast agent was injected until the patient felt fullness, and ultrasound (B-mode) was used to confirm whether the contrast agent filled the main canal and secondary and tertiary ducts. Then, power Doppler ultrasound was performed to determine whether the salivary gland had increased blood flow.RESULTS: In 2 cases in this report, a power Doppler ultrasound scan showed a significant increase in blood flow after contrast medium injection, which was not observed on a preoperative scan.CONCLUSION: Power Doppler ultrasound was found to be a simple, safe, and effective tool for real-time sialography monitoring.

Rapid evaluation of vasodilation efficacy of Angelica sinensis by near infrared spectroscopy based on quality markers / 中草药

Objective: By screening the quality markers of Ca2+ antagonistic ingredients, a rapid evaluation system about the vasodilatory effect of Angelica sinensis (AS) by near infrared spectroscopy (NIR) was established. Methods: The Ca2+ antagonists in AS were screened by UPLC/Q-TOF combined with Ca2+ double luciferase reporter gene system. To establish the quality markers, the antagonistic effects were further evaluated in cells and in vitro. The quality markers in multi batches of AS were quantitatively analyzed, and the corresponding NIR was obtained, and then the NIR fitting algorithm was established. Meanwhile, the relationship between Ca2+ antagonistic holistic activity of AS extract and the content of quality markers was investigated, and the prediction model for vasodilation efficacy of AS was constructed based on quality markers check analysis via NIR technique. Results: The screening result showed that ligustilide (X1) and levistilide A (X2) in AS had significant Ca2+ antagonistic effects, and the change of the content was consistent with the capacity of Ca2+ antagonistic action of AS extracts, so they were confirmed as quality markers. According to nonlinear regression analysis, the relationship between Ca2+ antagonistic effect (Y) of AS and the content of two quality markers satisfied the following functions: Y = 31.257 9 X1 + 381.352 0 X2 - 248.979 0 X1X2 + 18.482 2. In addition, the measured values from NIR simulation method for ligustilide and levistilide A detection showed a good correlation with the predicted values. Conclusion: In this study, it was found that ligustilide and levistilide A were quality markers responsible for vasodilation efficacy in AS, and the quantitative correlation between quality markers and the function of vasodilation effect was established. With the help of NIR technology, a novel solution for the rapid monitoring of the quality of traditional Chinese medicine was demonstrated.

Study on Vasodilatory Effect of Oxysophocarpine on Isolated Thoracic Aortic Rings of Rats and Its Mechanism / 中国药房

OBJECTIVE： To study the vasodilatory effect of oxysophocarpine （OSC） on isolated thoracic aortic rings of rats and its possible mechanism. METHODS： Thoracic aortic rings of rats were collected （called “vascular ring” for short）. Using K-H nutrient solution as blank control and the diastolic rate as index， the effects of different concentrations （0.2-1.0 mg/mL） of OSC on normal vascular rings in basal state， normal or endothelium-free vascular rings pre-contracted by norepinephrine （PE， 1×10－6 mol/L） were investigated. After pre-culturing normal thoracic aortic rings by nitric oxide synthase inhibitor L-nitro-arginine methyl ester（L-NAME）and cyclooxygenase inhibitor indomethacin（INDO），as well as pre-culturing endothelium-free vascular rings by potassium ion channel blocker BaCl2，tetraethylammonium（TEA）and 4-aminopyridine（4-AP）， the diastolic effects of OSC of different concentrations （0.2-1.0 mg/mL） on the above vascular rings were investigated by using the same method. RESULTS： Compared with blank control， there was no significant effects of different concentrations of OSC on the diastolic rate of normal vascular rings in basal state （P＞0.05）， but 0.4-1.0 mg/mL OSC could significantly improve the diastolic rate of normal or endothelium-free vascular rings pre-contracted by PE （P＜0.01）， in concentration-dependent manner. After preculturing with L-NAME， INDO， 4-AP and BaCl2， different concentrations of OSC had no significant effect on the diastolic rate of normal or endothelium-free vascular rings pre-contracted by PE （P＞0.05）. After pre-culturing with TEA and Gli， 0.4-1.0 mg/mL OSC could significantly reduce the diastolic rate of endothelium-free vas- cular rings pre-contracted by PE （P＜0.01）. CONCLUSIONS： OSC did not significantly dilate the thoracic aortic rings of rats in the basal state within the dose range （0.2-1.0 mg/mL）， but OSC of 0.4-1.0 mg/mL have significant diastolic effects on the normal or endothelium-free thoracic aortic rings of rats pre-contracted with PE. The mechanism of thoracic aortic rings dilation is endothelium-independent， which may be associated with receptor operational calcium channel，Ca2+-activated potassium channels and ATP-sensitive potassium channels.

Study on the Vasodilatory Effect Mechanism of Psoralen and Bakuchiol / 中国药房

OBJECTIVE： To investigate the vasodilatory effect mechanism of psoralen and bakuchiol. METHODS： The rat thoracic aorta was isolated to prepare vascular rings and de-endothelium vascular rings. Using contraction rate as index， the intact endothelium or de-endothelium vascular rings were pre-incubated with N-nitro-L-arginine methyl ester （L-NAME， 100 μmol/L）； vasodilatory effect of low-dose， medium-dose and high-dose of psoralen or bakuchiol（0.1，1，10 μmol/L）on aortic vessels pre- contracted with norepinephrine （NE， 1 μmol/L） or potassium chloride （KCl， 60 mmol/L） were investigated. The de-endothelium vascular rings were pre-incubated with calcium dependent potassium channel inhibitors tetraethylammonium chloride （TEA， 0.1 mmol/L） and inward rectifying potassium channel inhibitor barium chloride （BaCl2，0.1 mmol/L）； vasodilatory effect of low-dose， medium-dose and high-dose of bakuchiol （0.1， 1， 10 μmol/L） on de-endothelium vascular vessels pre-contracted with NE （1 μmol/L） were investigated. The microvascular endothelial cells were isolated by collagenase-neutral protease digestion； the effects of low-dose， medium-dose and high-dose of psoralen or bakuchiol （0.1， 1， 10 μmol/L） on the expression of eNOS protein were studied by ELISA. RESULTS： Psoralen and bakuchiol could significantly reduce the contraction rate of endothelium-intact aortic rings pre-contracted with NE（P＜0.01）； medium-dose and high-dose of psoralen and bakuchiol could significantly reduce the contraction rate of  endothelium-intact aortic rings pre-contracted with KCl（P＜0.05 or P＜0.01）； while the contraction rate could be increased by de-endothelium and NOS inhibition significantly （P＜0.05 or P＜0.01）. The medium-dose and high-dose of bakuchiol could significantly reduce the contraction rate of  de-endothelium vascular vessels pre-contracted with NE （P＜0.05 or P＜0.01）. The contraction rate could be increased by inhibiting inward rectifier potassium channels in vascular smooth muscle （P＜0.01）. Different dosages of psoralen and bakuchiol could significantly increase the expression levels of eNOS protein in rat cardiac microvascular endothelial cells（P＜0.01）. CONCLUSIONS： Psoralen and bakuchiol may play a role in vasodilation via endothelium-dependent NO pathway and by promoting eNOS protein expression in endothelial cells； bakuchiol may play a role in vasodilation via non-endothelium dependent pathway as opening inward rectifying potassium channel.