Protective effects of baicalin on experimental myocardial infarction in rats

Abstract Objective: This study aimed to investigate the protective effects of baicalin on myocardial infarction in rats and explore the related mechanisms. Methods: Fifty Sprague Dawley rats were randomly divided into the control, model, and low-, medium- and high-dose baicalin groups. The latter 3 groups were intraperitoneally injected with baicalin, with a dose of 12.5, 25 and 50 mg/kg, respectively. Then, the myocardial infarction model was established. The hemodynamic of rats was tested, the serum lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined, the myocardial superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected, and the myocardial B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X (Bax) protein expressions were determined. Results: Compared with the model group, in the high-dose baicalin group the ST segment height and LVEDP were significantly decreased (P<0.05), the LVSP was significantly increased (P<0.05), the serum LDH, CK-MB and TXA2 levels were significantly decreased (P<0.05), the PGI2 level was significantly increased (P<0.05), the myocardial SOD level was significantly increased (P<0.05), and the myocardial MDA level was significantly decreased (P<0.05); the myocardial Bcl-2 protein level was significantly increased, and the Bax protein level was significantly decreased (P<0.05). Conclusion: Baicalin has protective effects on myocardial infarction in rats. The possible mechanisms may be related to its resistance to oxidative stress, and up-regulation of Bcl-2 protein expression and down-regulation of Bax protein expression in myocardial tissue.

The effects of inhaled NO on plasma vasoactive factor and CTnI level in rabbits with acute massive pulmonary embolism

Abstract Purpose: To investigate changes in the plasma concentrations of cardiac troponin I (CTnI), thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and endothelin-1 (ET-1) in rabbits with massive pulmonary embolism (AMPE) and the impact of nitric oxide inhalation (NOI) on these indices. Methods: A total of 30 Japanese rabbits were used to construct an MPE model and were divided into 3 groups equally (n=10), including an EXP group (undergoing modeling alone), an NOI group (receiving NOI 2 h post-modeling) and a CON group (receiving intravenous physiological saline). Results: In the model group, plasma concentration of CTnI peaked at 16 h following modeling (0.46±0.10 µg/ml) and significantly decreased following NOI. Plasma levels of TXB2, PGI2 and ET-1 peaked at 12, 16 and 8 h following modeling, respectively, and significantly decreased at different time points (0, 2, 4, 8, 12, 16, 20 and 24 h) following NOI. A significant correlation was observed between the peak plasma CTnI concentration and peak TXB2, 6-keto prostaglandin F1α and ET-1 concentrations in the model and NOI groups. Conclusion: Increases in plasma TXA2, PGI2 and ET-1 levels causes myocardial damage in a rabbit model of AMPE; however, NOI effectively down regulates the plasma concentration of these molecules to produce a myocardial-protective effect.

Protective effect of dexmedetomidine against myocardial ischemia-reperfusion injury in rabbits

Abstract Purpose: To investigate the influence of dexmedetomidine on myocardial ischemia-reperfusion injury (IRI) in rabbits. Methods: Twenty-four New Zealand white rabbits were randomly divided into two equal-sized groups: IRI group (group IR) and dexmedetomidine group (group D). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular diastolic pressure (LVDP), +dp/dtmax, -dp/dtmax, and t-dp/dtmax were recorded and calculated at the following time points: before (T0) and after (T1) dexmedetomidine infusion, after 30-min ischemia (T2), and after 120-min reperfusion (T3). The levels of plasma endothelin 1 (ET-1), thromboxane A2 (TXA2), and platelet activating factor (PAF); area of myocardial infarction (MI); and no-reflow area were evaluated. Results: SBP, DBP, LVSP, LVEDP, LVDP, and +dp/dtmax at T3 were higher in group D than in group IR (P<0.05). The average no-reflow area in group IR was significantly smaller than that in group D (14±3% vs. 38±5%, P=0.0116). The ET-1, TXA2, and PAF levels at T2 and T3 were higher than those at T0 in both groups (P<0.05). Conclusion: Dexmedetomidine could reduce the magnitude of ischemic myocardial no-reflow area and protect the myocardium with ischemia-reperfusion injury.

Antiplatelet and Antithrombotic Effects of the Extract of Lindera obtusiloba Leaves

Lindera obtusiloba has been used in traditional herbal medicine for the treatment of blood stasis and inflammation. The leaves of Lindera obtusiloba have been reported to exhibit various physiological activities. However, there is little information available on their antiplatelet and antithrombotic activities. Thus, the present study aimed to evaluate the effect of Lindera obtusiloba leaf extract (LLE) on platelet activities, coagulation and thromboembolism. In a platelet aggregation study, LLE significantly inhibited various agonist-induced platelet aggregations in vitro and ex vivo. Furthermore, LLE significantly inhibited collagen-induced thromboxane A2 (TXA2) production in rat platelets. In addition, oral administration of LLE was protective in a mouse model of pulmonary thromboembolism induced by intravenous injection of a mixture of collagen and epinephrine. Interestingly, LLE did not significantly alter prothrombin time (PT) and activated partial thromboplastin time (aPTT). This study indicates that the antithrombotic effects of LLE might be due to its antiplatelet activities rather than anticoagulation. Taken together, these results suggest that LLE may be a candidate preventive and therapeutic agent in cardiovascular diseases associated with platelet hyperactivity.

Daño a células endoteliales en cultivo inducido por el isoprostano 8-iso-PGF2a / Damage to cultured endothelial cells induced by isoprostane 8-iso PGF2

INTRODUCCIÓN: el endotelio vascular posee un papel esencial en los procesos asociados a la enfermedad cardiovascular. Existe estrecha relación entre el desbalance redox de estas células y la aparición y evolución de estas enfermedades. Entre los marcadores de daño oxidativo a los lípidos de membranas se encuentra el isoprostano 8-iso-PGF2a, que aumenta en estos pacientes. OBJETIVO: evaluar el efecto del isoprostano 8-iso-PGF2a sobre células endoteliales en cultivo y la protección con la proteína de estrés térmico a-cristalina. MÉTODOS: se cultivaron células endoteliales de la línea H5V y se evaluó el efecto del isoprostano 8-iso-PGF2a y del análogo del tromboxano A2, U46619, sobre la supervivencia celular. Se evaluó el efecto protector de la proteína de estrés térmico a-cristalina a través de la incubación de los cultivos con 1 mg/ml de la proteína previo a la inducción del daño con los compuestos en estudio. RESULTADOS: la supervivencia celular disminuyó proporcional al aumento de la concentración del isoprostano y del U46619. La a-cristalina aumentó la supervivencia celular en un 20 % al preincubar los cultivos sometidos al efecto de ambos compuestos. CONCLUSIONES: el isoprostano 8-iso-PGF2a, además, de ser un marcador de daño oxidativo puede ser considerado un inductor directo de daño a las células del endotelio vascular, efecto mediado a través, de la generación de tromboxano A2 o la activación de su receptor. La proteína de estrés térmico a-cristalina, añadida de forma exógena, puede considerarse un protector endotelial.

INTRODUCTION: the vascular endothelium plays an essential role in processes associated with cardiovascular disease. There is a close relationship between redox imbalance in these cells and the appearance and evolution of such diseases. Increased isoprostane 8-iso PGF2 is among the markers of oxidative damage to membrane lipids in these patients. OBJECTIVE: evaluate the effect of isoprostane 8-iso PGF2 on cultured endothelial cells and the protection provided by -crystallin heat-shock stress protein. METHODS: endothelial cells from line H5V were cultured to evaluate the effect of isoprostane 8-iso PGF2 and thromboxane A2 analog U46619 on cell survival. An evaluation was conducted of the protective effect of -crystallin heat-shock stress protein by incubation of the cultures with 1 mg/ml of the protein prior to damage induction with the study compounds. RESULTS: cell survival decreased as isoprostane and U46619 concentration increased. -Crystallin increased cell survival by 20% upon preincubation of the cultures subjected to both compounds. CONCLUSIONS: besides being an oxidative damage marker, isoprostane 8-iso PGF2 may be considered a direct inducer of damage to vascular endothelial cells. This effect is mediated by the generation of thromboxane A2 or the activation of its receptor. Added exogenously, -crystallin heat-shock stress protein may be considered to be an endothelial protector.

Interrelación del equilibrio tromboxano A2-prostaciclina y su modificación cuando se ingiere aspirina / Interrelation of the balance tromboxano A2-prostaciclina and its modification when aspirin is ingested

Introducción: la aspirina, es usada por su acción antiinflamatoria, analgésica, antipirética y antiagregante plaquetaria. El conocimiento del metabolismo del ácido araquidónico es fundamental para el estomatólogo que basa su trabajo en diagnosticar y tratar procesos inflamatorios en tejidos bucodentales, también por su condición de cirujano debe estar alerta en no realizar intervenciones quirúrgicas en pacientes que estén tomando aspirina, por interrumpir este medicamento la agregación plaquetaria, importante paso de la hemostasia normal. Objetivo: interpretar la interrelación hemostática del tromboxano A2 y la prostaciclina en condiciones fisiológicas, y el resultado de su modificación cuando se ingiere aspirina. Método: PubMed fue empleada como fundamental fuente de búsqueda, que incluyó el conocimiento sobre el fármaco aspirina, la interacción del tromboxano y la prostaclina, y la acción que sobre el equilibrio de estos productos ejerce la aspirina; también se revisaron HINARI, LILACS y Medline. Desarrollo: el ácido araquidónico es un ácido graso poliinsaturado de 20 átomos de carbono (ácido 5, 8, 11, 14-eicosatetraenoico) que procede directamente de la dieta. La relación recíproca entre PG-I2 y el TxA2 constituye un mecanismo finamente equilibrado que sirve para regular la función plaquetaria del ser humano. La utilidad de la aspirina en los pacientes expuestos a trombogénesis se debe, en gran parte, a su capacidad para inhibir la síntesis del TxA2, agente derivado del ácido araquidónico, elemento que se encuentra esterificado a los fosfolípidos de la membrana plaquetaria. El óxido nítrico, igual que la PG-I2, actúa también como vasodilatador e inhibidor de la agregación plaquetaria. Conclusiones: los pacientes que acuden al estomatólogo y por prescripción facultativa están tomando aspirina, tienen su sistema plaquetario inhibido y no pueden sintetizar tromboxano. El proceder quirúrgico por parte del estomatólogo en un paciente que esté ingiriendo aspirina lo expone al desarrollo de hemorragia de causa iatrogénica(AU)

Introduction: aspirin is used by its arachidonic acid is fundamental for the dentist that bases its work on diagnosis and treatment of inflammatory processes, also for its surgeon condition he should be alert to do not carry out surgical interventions in patients that are taking aspirin, because this drug interrupts platelet aggregation, important step of the normal hemostasis. Objective: to interpret the hemostatic interrelation of the tromboxano A2 and the prostaciclina in physiologic conditions and the result of their modification when aspirin is ingested. Method: it was employee as fundamental search source the PubMed, other databases also revised they were HINARI, LILACS, Medline. Was carried out a search that included the knowledge on the drug aspirin, the interaction of the tromboxano and the prostaclina, and the action that it has more than enough the balance of these products it exercises the aspirin. Development: the arachidonic acid is a polyunsaturated fatty acid of 20 atoms of carbon (5, 8, 11, 14-eicosatetraenoic acid) that proceeds directly from diet. The reciprocal relationship between PG-I2 and TxA2 constitutes a finely balanced mechanism that is good to regulate the human being's platelet function. The utility of aspirin in patients exposed to thrombogenesis is largely due to its capacity to inhibit the synthesis of the TxA2, agent derived from arachidonic acid, which is esterified to the phospholipids of the platelet membrane. Nitric oxide, the same as the PG-I 2, also acts as vasodilator and inhibitor of the platelet aggregation. Conclusions: the patients that go to the dentist and for medical prescription are taking aspirin, have their platelet system inhibited and cannot synthesize tromboxane. Surgical processes performed by the dentist in a patient that is ingesting aspirin exposes him to the development of hemorrhage of yatrogenic cause(AU)

Dual effect of atorvastatin on endothelium; reduction In LDL And TXA2 levels but unaltered HCY levels In obese hyperlipidemic rats

Objective: The objective of the study was to observe the effect of lipid lowering therapy on homocysteine and TXA[2] concentration in obese hyperlipidemic Sprague Dawley rats

Design: Randomized Control Trial [RCT]

Place and Duration of study: The study was conducted in Department of Physiology and Centre for Research in Experimental and Applied Medicine [CREAM], Army Medical College, Rawalpindi; and National Institute of Health [NIH] Islamabad over a period of 12 months

Methodology: Ninety healthy Sprague Dawley rats divided into three equal groups. Group I [n=30] were healthy controls, group II [n=30] were made obese and group III [n=30] were obese treated [atorvastatin 10 mg/kg/day orally by gavage method for three weeks]. Body weight was recorded thrice weekly, lipid profile was measured by colorimetric method on microlab and homocysteine and TXA2 were measured by Enzyme Linked Immunosorbant Assay

Results: Serum low density lipoproteins and TXA2 decreased after three weeks of atorvastatin administration, elevated HCY concentration in obese hyperlipidemic rats however was not significantly affected

Conclusion: Atorvastatin apart from lowering lipid levels in the body also reduces TXA[2] concentration which is a vasoprotective. Elevated HCY concentration which is deleterious to the endothelium however is not affected

Inhibitory effects and mechanisms of snake venom tripeptide pENW on platelet adhesion / 药学学报

This study was designed to investigate inhibitory effects and possible mechanisms of snake venom tripeptide (pENW) on platelet adhesion in order to promote the development of a novel anti-platelet therapy. To study the inhibitory effects of pENW on platelet adhesion, washed platelets pre-incubated with pENW (116.5-466.2 μmol x L(-1)) were used to test the ability of platelet adhesion to fibrinogen. Effect of pENW on fibrin clot retraction was also tested. Effect of pENW on platelets viability was tested by MTT assay. Effect of pENW on reactive-oxygen species (ROS) levels of platelet was studied by flow cytometry assay. Calcium mobilization in Fura-2/AM-loaded platelets was monitored with a spectrofluorimeter. Cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP), thromboxane A2 (determined as its metabolite thromboxane B2) were measured using enzyme immunoassay kits. Akt, ERK and p38 phosphorylation were tested by Western blot. The results showed that pENW inhibited platelet adhesion and fibrin clot retraction in a concentration-dependent manner without cytotoxicity. Intracellular cGMP and cAMP in both resting and thrombin-activated platelets were increased by pENW. In addition, pENW attenuated intracellular Ca2+ mobilization and TXA2 production in platelets stimulated by thrombin. As shown by Western blot assay, Akt, ERK and p38 phosphorylation in thrombin-induced platelet were attenuated by pENW. However, inhibitory effects of pENW had nothing to do with ROS. Thus, pENW exhibited a significant inhibition on platelet adhesion to fibrinogen, which means pENW could block the first step of thrombosis as while as retard the more stable clot formation. The mechanisms of pENW on inhibition platelet adhesion might be related to instant regulations, such as protein kinases.

Impacts of high-volume hemofiltration on hemodynamics and vascular endothelial permeability in children with septic shock / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effects of high-volume hemofiltration (HVHF) on hemodynamics, vasoactive factors, and vascular endothelial permeability in children with septic shock by a comparative analysis.</p><p><b>METHODS</b>Thirty-six children who were diagnosed with septic shock between January 2013 and September 2014 were randomly divided into control and observation groups (n=18 each). Children in the control group were treated with the standard-volume hemofiltration (SVHF), while children in the observation group were treated with HVHF. The hemodynamic indices and levels of vasoactive factors including 6-keto-prostaglandin F1α (6-keto-PGF1α), thromboxane B2 (TXB2), soluble E-selectin (sE-selectin), and endothelium-derived relaxing factor (EDRF) were determined before and after treatment. In addition, the effects of ultrafiltrate on endothelial cell permeability were assessed.</p><p><b>RESULTS</b>Compared with the control group, the observation group had significantly higher mean arterial pressure, significantly higher blood oxygen saturation, and a significantly lower heart rate after treatment (P<0.05). The levels of TXB2 and sE-selectin were significantly lower in the observation group than in the control group (P<0.05), while the levels of 6-keto-PGF1α and EDRF were significantly higher in the observation group than in the control group (P<0.05). Compared with the control group, the ultrafiltrate significantly attenuated the transepithelial electrical resistance in the observation group (P<0.05).</p><p><b>CONCLUSIONS</b>Compared with SVHF, HVHF is a more effective approach for improving the hemodynamics and levels of vasoactive factors and reducing the vascular endothelial permeability in children with septic shock.</p>

Nicotine in High Concentration Causes Contraction of Isolated Strips of Rabbit Corpus Cavernosum

It is well known that cigarette smoke can cause erectile dysfunction by affecting the penile vascular system. However, the exact effects of nicotine on the corpus cavernosum remains poorly understood. Nicotine has been reported to cause relaxation of the corpus cavernosum; it has also been reported to cause both contraction and relaxation. Therefore, high concentrations of nicotine were studied in strips from the rabbit corpus cavernosum to better understand its effects. The proximal penile corpus cavernosal strips from male rabbits weighing approximately 4 kg were used in organ bath studies. Nicotine in high concentrations (10(-5)~10(-4) M) produced dose-dependent contractions of the corpus cavernosal strips. The incubation with 10(-5) M hexamethonium (nicotinic receptor antagonist) significantly inhibited the magnitude of the nicotine associated contractions. The nicotine-induced contractions were not only significantly inhibited by pretreatment with 10(-5) M indomethacin (nonspecific cyclooxygenase inhibitor) and with 10(-6) M NS-398 (selective cyclooxygenase inhibitor), but also with 10(-6) M Y-27632 (Rho kinase inhibitor). Ozagrel (thromboxane A2 synthase inhibitor) and SQ-29548 (highly selective TP receptor antagonist) pretreatments significantly reduced the nicotine-induced contractile amplitude of the strips. High concentrations of nicotine caused contraction of isolated rabbit corpus cavernosal strips. This contraction appeared to be mediated by activation of nicotinic receptors. Rho-kinase and cyclooxygenase pathways, especially cyclooxygenase-2 and thromboxane A2, might play a pivotal role in the mechanism associated with nicotine-induced contraction of the rabbit corpus cavernosum.

Effect of Magnesium Sulfate, Nifedipine Tablet Combined Salvia Injection on ET-1/NO, TXA2/PGI2 and Hemorheology of Preeclampsia Patients / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of magnesium sulfate, Nifedipine Tablet (NT) combined Salvia Injection (SI) on endothelin-1 (ET-1), nitric oxide (NO), thromboxane A2(TXA2), prostacyclin I2(PG2), and hemorheology of preeclampsia patients.</p><p><b>METHODS</b>Totally 704 preeclampsia patients were randomly assigned to the treatment group and the control group, 352 cases in each group. All patients were treated with magnesium sulfate combined NT (on the first day: slow intravenous injection of magnesium sulfate 5 g + intravenous dripping of magnesium sulfate injection 10 g + oral administration of NT 30 mg; on the second and third day, intravenous dripping of magnesium sulfate injection 10 g + oral administration of NT 30 mg), while those in the treatment group were dripped with SI additionally at 20 mL per day for 3 consecutive days. Before and after treatment plasma levels of endothelin-1 (ET-1), nitric oxide (NO), TXA2, PGi2, and hemorheology indicators [such as high blood viscosity (HBV), low blood viscosity (LBV), plasma viscosity (PV), erythrocyte rigidity index (ERI), fibrinogen (FIB)] of two groups were detected.</p><p><b>RESULTS</b>Compared with the same group before treatment, serum levels of ET-1, TXA2, HBV, LBV, PV, ERI, and FIB decreased in the two groups after treatment (P <0. 05), but levels of NO and PG2 increased (P <0. 05). Compared with the control group in the same period, levels of ET-1, TXA2, HBV, LBV, PV, ERI, and FIB decreased in the treatment group after treatment (P <0. 05), but levels of NO and PGI2 increased (P <0. 05).</p><p><b>CONCLUSION</b>Magnesium sulfate, NT combined SI could effectively regulate the balance of ET-1/NO and TXA2/PGI2, and improve hemorheology of preeclampsia patients.</p>

The relaxing effect of Poncirus fructus and its flavonoid content on porcine coronary artery / 한국실험동물학회지

Coronary artery disease is a common occurrence in human, and causes enormous social cost. Poncirus fructus (PF), the dried immature fruits of Poncirus trifoliata Rafinesquem, is used in the treatment of womb contraction and dyspepsia, as a prokinetic, and in improving blood circulation. This study was performed to investigate the effects of PF and some of its flavonoids components on the coronary from the pig. The arterial ring was suspended by a pair of stainless steel stirrups in an organ bath. The end of the upper stirrup was connected to an isometric force transducer. A dose-dependent induction of relaxation was observed by both water and 70% ethanol extracts of PF in the porcine coronary artery precontracted with U46619 (100 nM), a stable analogue of the potent vasoconstrictor thromboxane A2. The 70% ethanol extract showed more efficacy than the water extract. Pretreatment of the artery with L-NAME (100 microM), a nitric oxide synthase inhibitor, resulted in a significant reduction in the relaxation induced by PF extract. In addition, ODQ (10 microM), a soluble guanylate cyclase inhibitor, also significantly reduced the effects of PF extracts. Hesperidin, a flavonoid present in PF, induced very weak relaxation of the porcine coronary artery at a high concentration (100 microM), while its aglycone, hesperetin, demonstrated a dose-dependent relaxation. In conclusion, PF extracts induced relaxation in the porcine coronary artery, partially through the nitric oxide-cGMP pathway, and the aglycones of flavonoids might be also involved in the relaxation of the same artery.

Cordycepin-Enriched WIB801C from Cordyceps militaris Inhibits Collagen-Induced Ca2+i Mobilization via cAMP-Dependent Phosphorylation of Inositol 1, 4, 5-Trisphosphate Receptor in Human Platelets

In this study, we prepared cordycepin-enriched (CE)-WIB801C, a n-butanol extract of Cordyceps militaris-hypha, and investigated the effect of CE-WIB801C on collagen-induced human platelet aggregation. CE-WIB801C dose-dependently inhibited collagen-induced platelet aggregation, and its IC50 value was 175 microg/ml. CE-WIB801C increased cAMP level more than cGMP level, but inhibited collagen-elevated [Ca2+]i mobilization and thromboxane A2 (TXA2) production. cAMP-dependent protein kinase (A-kinase) inhibitor Rp-8-Br-cAMPS increased the CE-WIB801C-downregulated [Ca2+]i level in a dose dependent manner, and strongly inhibited CE-WIB801C-induced inositol 1, 4, 5-trisphosphate receptor (IP3R) phosphorylation. These results suggest that the inhibition of [Ca2+]i mobilization by CE-WIB801C is resulted from the cAMP/A-kinase-dependent phosphorylation of IP3R. CE-WIB801C suppressed TXA2 production, but did not inhibit the activities of cyclooxygenase-1 (COX-1) and TXA2 synthase (TXAS). These results suggest that the inhibition of TXA2 production by WIB801C is not resulted from the direct inhibition of COX-1 and TXAS. In this study, we demonstrate that CE-WIB801C with cAMP-dependent Ca2+-antagonistic antiplatelet effects may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

The Inhibitory Effect of Apigenin on the Agonist-Induced Regulation of Vascular Contractility via Calcium Desensitization-Related Pathways

Apigenin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of apigenin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Apigenin significantly relaxed fluoride-, thromboxane A2 mimetic- or phorbol ester-induced vascular contraction, which suggests that apigenin could be an anti-hypertensive that reduces agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, apigenin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels, which suggests the mechanism involving the inhibition of Rho-kinase and MEK activity and the subsequent phosphorylation of MYPT1 and ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of apigenin on agonist-induced vascular contraction regardless of endothelial function.

Reactivity of intrapulmonary arterial rings to thromboxane A2 and endothelin-1 is reduced in patients with chronic obstructive pulmonary disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the reactivity of intrapulmonary arterial rings to vasoactive substances as thromboxane A2 and endothelin-1 in patients with chronic obstructive pulmonary disease (COPD).</p><p><b>METHODS</b>Intrapulmonary arterial rings isolated from patients with normal lung function and COPD were mounted in a Multi Myograph system to determine the reactivity of the intrapulmonary arterial rings to 60 mmol/L KCl, thromboxane A2 analogue U46619 and endothelin-1 before and after preconditioning with the COX synthase inhibitor indomethacin.</p><p><b>RESULTS</b>The reactivity of intrapulmonary arterial rings to U46619 and endothelin-1 was significantly decreased in patients with COPD. The reactivity to U46619 was dramatically decreased in patients with normal lung function after application of indomethacin.</p><p><b>CONCLUSION</b>The reactivity of intrapulmonary arterial rings is significantly decreased in patients with COPD.</p>

The Inhibitory Effect of Eupatilin on the Agonist-Induced Regulation of Vascular Contractility

The present study was undertaken to investigate the influence of eupatilin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Eupatilin more significantly relaxed fluoride-induced vascular contraction than thromboxane A2 or phorbol ester-induced contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, eupatilin significantly inhibited fluoride-induced increases in pMYPT1 levels. On the other hand, it didn't significantly inhibit phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the primarily inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1. This study provides evidence regarding the mechanism underlying the relaxation effect of eupatilin on agonist-induced vascular contraction regardless of endothelial function.

Disappearance of Hypoxic Pulmonary Vasoconstriction and O2-Sensitive Nonselective Cationic Current in Arterial Myocytes of Rats Under Ambient Hypoxia

Acute hypoxia induces contraction of pulmonary artery (PA) to protect ventilation/perfusion mismatch in lungs. As for the cellular mechanism of hypoxic pulmonary vasoconstriction (HPV), hypoxic inhibition of voltage-gated K+ channel (Kv) in PA smooth muscle cell (PASMC) has been suggested. In addition, our recent study showed that thromboxane A2 (TXA2) and hypoxia-activated nonselective cation channel (I(NSC)) is also essential for HPV. However, it is not well understood whether HPV is maintained in the animals exposed to ambient hypoxia for two days (2d-H). Specifically, the associated electrophysiological changes in PASMCs have not been studied. Here we investigate the effects of 2d-H on HPV in isolated ventilated/perfused lungs (V/P lungs) from rats. HPV was almost abolished without structural remodeling of PA in 2d-H rats, and the lost HPV was not recovered by Kv inhibitor, 4-aminopyridine. Patch clamp study showed that the hypoxic inhibition of Kv current in PASMC was similar between 2d-H and control. In contrast, hypoxia and TXA2-activated I(NSC) was not observed in PASMCs of 2d-H. From above results, it is suggested that the decreased I(NSC) might be the primary functional cause of HPV disappearance in the relatively early period (2 d) of hypoxia.

Inhibitory Effects of Epigallocatechin-3-Gallate on Microsomal Cyclooxygenase-1 Activity in Platelets

In this study, we investigated the effect of (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins from green tea leaves, on activities of cyclooxygenase (COX)-1 and thromboxane synthase (TXAS), thromboxane A2 (TXA2) production associated microsomal enzymes. EGCG inhibited COX-1 activity to 96.9%, and TXAS activity to 20% in platelet microsomal fraction having cytochrome c reductase (an endoplasmic reticulum marker enzyme) activity and expressing COX-1 (70 kDa) and TXAS (58 kDa) proteins. The inhibitory ratio of COX-1 to TXAS by EGCG was 4.8. These results mean that EGCG has a stronger selectivity in COX-1 inhibition than TXAS inhibition. In special, a nonsteroid anti-inflammatory drug aspirin, a COX-1 inhibitor, inhibited COX-1 activity by 11.3% at the same concentration (50 microM) as EGCG that inhibited COX-1 activity to 96.9% as compared with that of control. This suggests that EGCG has a stronger effect than that of aspirin on inhibition of COX-1 activity. Accordingly, we demonstrate that EGCG might be used as a crucial tool for a strong negative regulator of COX-1/TXA2 signaling pathway to inhibit thrombotic disease-associated platelet aggregation.

Mechanisms of Platelet Activation and Integrin alphaIIbeta3

Platelet aggregation is not only an essential part of hemostasis, but also initiates acute coronary syndrome or ischemic stroke. The precise understanding of the activation mechanism of platelet aggregation is fundamental for the development of more effective agents against platelet aggregation. Adenosine diphosphate, thrombin, and thromboxane A2 activate platelet integrin alphaIIbbeta3 through G protein-coupled receptors. G protein-mediated signaling pathways, which are initiated by Gq, G12/G13 or Gi, include phospholipase C with calcium signaling, Rho signaling, protein kinase C and phosphatidylinositol 3-kinase. Rap1b, Ca2+ and diacylglycerol-regulated guanine nucleotide exchange factor I, Rap1-GTP-interacting adaptor molecule, and Akt are important proteins involved in G protein-mediated activation of integrin alphaIIbbeta3. Binding of talin-1 and kindlin-3 to cytoplasmic domains of beta3-integrin triggers a conformational change in the extracellular domains that increases its affinity for ligands, such as fibrinogen or von Willebrand factor. Fibrinogens act as bridges between adjacent platelets to generate a platelet aggregate.

Effects of electro-acupuncture combined general anesthesia on myocardial injury of high blood sugar patients with coronary heart disease in the perioperative phase / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effects of electro-acupuncture (EA) combined general anesthesia on myocardial injury of high blood sugar patients with coronary heart disease (CHD) in the perioperative phase.</p><p><b>METHODS</b>Recruited were 40 senile patients with glycosylated hemoglobin (HbA1c) more than 6.5%. They were more than 60 years old. They received post-traumatic fracture reduction surgery of four limbs. They were randomly assigned to two groups, Group N (treated by general intravenous anesthesia) and Group D (treated by EA combined with general intravenous anesthesia), 20 in each group. All patients were maintained anesthesia by propofol, fentanyl, and vecuronium. Prior to the induction of anesthesia, patients in Group D received induction of EA at Neiguan (PC6) and Baihui (DU20) for 20 min, which lasted to the end of the surgery. At before intubation (T0), immediately after intubation (T1), 5 min (T2), immediately after extubation (T3), 5 min (T4), 60 min (T5), 180 min (T6), the fast blood glucose (FBG), plasma vasoactive substance TXB2 and 6-K-prostacycline (6-K-PGF1alpha) were detected in the two groups. The glucose coefficient of variation (GluCV) and the ratio of TXB2/6-K-PGF1alpha were calculated. The changes of ST-segment elevation (mV, sampling 1 min after each time point, and the mean calculated) was recorded.</p><p><b>RESULTS</b>There was no statistical difference in all the tested values between the two groups at T0 (P>0.05). The FBG, ST elevation, and the ratio of TXB2/6-K-PGF1alpha were significantly higher at each time point than at T0 in Group N (P<0.05), while there was no statistical difference in Group D (P>0.05). The ratio of TXB2/6-K-PGF1alpha and ST elevation were significantly higher in Group N than in Group D (P<0.01). The TXB2 and 6-K-PGF1alpha were significantly higher at each time point than at T0 in the two groups (P<0.05). The increment of TXB2 was obviously lower in Group D than in Group N (P<0.05), but the increment of 6-K-PGF1alpha was obviously higher in Group D than in Group N (P<0.05).</p><p><b>CONCLUSION</b>EA could reduce the perioperative stress response to the injury of coronary vascular endothelial cells, and improve myocardial ischemia and CHD patients' prognosis by regulating the central nervous system, the cardiovascular active substances, and anti-oxygen free radicals.</p>