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1.
J Toxicol Sci ; 49(6): 269-279, 2024.
Article in English | MEDLINE | ID: mdl-38825486

ABSTRACT

Although morphine has been used for treatment-resistant dyspnea in end-stage heart failure patients, information on its cardiovascular safety profile remains limited. Morphine was intravenously administered to halothane-anesthetized dogs (n=4) in doses of 0.1, 1 and 10 mg/kg/10 min with 20 min of observation period. The low and middle doses attained therapeutic (0.13 µg/mL) and supratherapeutic (0.97 µg/mL) plasma concentrations, respectively. The low dose hardly altered any of the cardiovascular variables except that the QT interval was prolonged for 10-15 min after its start of infusion. The middle dose reduced the preload and afterload to the left ventricle for 5-15 min, then decreased the left ventricular contractility and mean blood pressure for 10-30 min, and finally suppressed the heart rate for 15-30 min. Moreover, the middle dose gradually but progressively prolonged the atrioventricular conduction time, QT interval/QTcV, ventricular late repolarization period and ventricular effective refractory period without altering the intraventricular conduction time, ventricular early repolarization period or terminal repolarization period. A reverse-frequency-dependent delay of ventricular repolarization was confirmed. The high dose induced cardiohemodynamic collapse mainly due to vasodilation in the initial 2 animals by 1.9 and 3.3 min after its start of infusion, respectively, which needed circulatory support to treat. The high dose was not tested further in the remaining 2 animals. Thus, intravenously administered morphine exerts a rapidly appearing vasodilator action followed by slowly developing cardiosuppressive effects. Morphine can delay the ventricular repolarization possibly through IKr inhibition in vivo, but its potential to develop torsade de pointes will be small.


Subject(s)
Anesthetics, Inhalation , Halothane , Heart Rate , Morphine , Animals , Dogs , Morphine/administration & dosage , Heart Rate/drug effects , Anesthetics, Inhalation/administration & dosage , Anesthetics, Inhalation/pharmacokinetics , Male , Toxicokinetics , Dose-Response Relationship, Drug , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/pharmacokinetics , Blood Pressure/drug effects , Electrocardiography/drug effects , Female , Infusions, Intravenous , Vasodilation/drug effects , Electrophysiological Phenomena/drug effects
2.
BMC Cardiovasc Disord ; 24(1): 292, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840064

ABSTRACT

BACKGROUND: Tobacco use is recognized as a major cause of cardiovascular disease, which is associated with endothelial dysfunction. Endothelial function is evaluated using flow-mediated dilation (FMD), which is a noninvasive method. This meta-analysis aimed to investigate the association between smoking exposure and endothelial function evaluated using FMD values. METHODS: We searched the PubMed, Embase, Web of Science, and Cochrane Library databases for cohort studies of smokers or passive smokers that used FMD to assess endothelial function. The primary outcome of the study was the change in the rate of FMD. The risk of bias was evaluated using the Cochrane Collaboration tool and Newcastle-Ottawa Scale. Further, the weighted mean difference was used to analyze the continuous data. RESULTS: Overall, 14 of 1426 articles were included in this study. The results of these articles indicated that smoking is a major cause of endothelial dysfunction and altered FMD; a pooled effect size of - 3.15 was obtained with a 95% confidence interval of (- 3.84, - 2.46). Notably, pregnancy status, Asian ethnicity, or health status did not affect heterogeneity. CONCLUSIONS: We found that smoking has a significant negative impact on FMD, and measures such as medication or education for smoking cessation may improve endothelial function and reduce the risk of cardiovascular disease. TRIAL REGISTRATION: The meta-analysis was registered with PROSPERO on April 5th, 2023 (CRD42023414654).


Subject(s)
Cardiovascular Diseases , Endothelium, Vascular , Vasodilation , Humans , Endothelium, Vascular/physiopathology , Female , Male , Middle Aged , Adult , Risk Assessment , Cardiovascular Diseases/physiopathology , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/etiology , Cardiovascular Diseases/epidemiology , Aged , Risk Factors , Tobacco Smoke Pollution/adverse effects , Predictive Value of Tests , Smoking/adverse effects , Smoking/physiopathology , Young Adult , Smokers , Brachial Artery/physiopathology , Brachial Artery/diagnostic imaging , Heart Disease Risk Factors
3.
Redox Biol ; 73: 103189, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38788541

ABSTRACT

Age-related endothelial dysfunction is a pivotal factor in the development of cardiovascular diseases, stemming, at least in part, from mitochondrial dysfunction and a consequential increase in oxidative stress. These alterations are central to the decline in vascular health seen with aging, underscoring the urgent need for interventions capable of restoring endothelial function for preventing cardiovascular diseases. Dietary interventions, notably time-restricted feeding (TRF), have been identified for their anti-aging effects on mitochondria, offering protection against age-associated declines in skeletal muscle and other organs. Motivated by these findings, our study aimed to investigate whether TRF could similarly exert protective effects on endothelial health in the vasculature, enhancing mitochondrial function and reducing oxidative stress. To explore this, 12-month-old C57BL/6 mice were placed on a TRF diet, with food access limited to a 6-h window daily for 12 months. For comparison, we included groups of young mice and age-matched controls with unrestricted feeding. We evaluated the impact of TRF on endothelial function by measuring acetylcholine-induced vasorelaxation of the aorta. Mitochondrial health was assessed using fluororespirometry, and vascular reactive oxygen species (ROS) production was quantified with the redox-sensitive dye dihydroethidium. We also quantified 4-hydroxynonenal (4-HNE) levels, a stable marker of lipid peroxidation, in the aorta using ELISA. Our findings demonstrated that aged mice on a standard diet exhibited significant impairments in aortic endothelial relaxation and mitochondrial function, associated with elevated vascular oxidative stress. Remarkably, the TRF regimen led to substantial improvements in these parameters, indicating enhanced endothelial vasorelaxation, better mitochondrial function, and reduced oxidative stress in the aortas of aged mice. This investigation establishes a vital foundation, paving the way for subsequent clinical research aimed at exploring the cardiovascular protective benefits of intermittent fasting.


Subject(s)
Aging , Aorta , Endothelium, Vascular , Mitochondria , Oxidative Stress , Reactive Oxygen Species , Vasodilation , Animals , Mice , Mitochondria/metabolism , Endothelium, Vascular/metabolism , Endothelium, Vascular/drug effects , Reactive Oxygen Species/metabolism , Aorta/metabolism , Aorta/drug effects , Vasodilation/drug effects , Aging/metabolism , Male , Mice, Inbred C57BL , Aldehydes/metabolism , Aldehydes/pharmacology
4.
Biosci Rep ; 44(6)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38757914

ABSTRACT

Surgeries that require general anesthesia occur in 1.5-2% of gestations. Isoflurane is frequently used because of its lower possibility of affecting fetal growth. Therefore, we examined the isoflurane anesthesia-induced effects on maternal hemodynamic and vascular changes. We hypothesized that isoflurane would enhance endothelium-dependent vasodilation as a consequence of increased nitric oxide and decreased metalloproteinases (MMPs). Female rats (n=28) were randomized into 4 groups (7 rats/group): conscious (non-anesthetized) non-pregnant group, non-pregnant anesthetized group, conscious pregnant group, and pregnant anesthetized group. Anesthesia was performed on the 20th pregnancy day, and hemodynamic parameters were monitored. Nitric oxide metabolites, gelatinolytic activity of MMP-2 and MMP-9, and the vascular function were assessed. Isoflurane caused no significant hemodynamic changes in pregnant compared with non-pregnant anesthetized group. Impaired acetylcholine-induced relaxations were observed only in conscious non-pregnant group (by approximately 62%) versus 81% for other groups. Phenylephrine-induced contractions were greater in endothelium-removed aorta segments of both pregnant groups (with or without isoflurane) compared with non-pregnant groups. Higher nitric oxide metabolites were observed in anesthetized pregnant in comparison with the other groups. Reductions in the 75 kDa activity and concomitant increases in 64 kDa MMP-2 isoforms were observed in aortas of pregnant anesthetized (or not) groups compared with conscious non-pregnant group. Isoflurane anesthesia shows stable effects on hemodynamic parameters and normal MMP-2 activation in pregnancy. Furthermore, there were increases in nitric oxide bioavailability, suggesting that isoflurane provides protective actions to the endothelium in pregnancy.


Subject(s)
Isoflurane , Matrix Metalloproteinase 2 , Nitric Oxide , Vasodilation , Animals , Female , Pregnancy , Rats , Anesthetics, Inhalation/pharmacology , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Hemodynamics/drug effects , Isoflurane/pharmacology , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Nitric Oxide/metabolism , Vasodilation/drug effects , Rats, Wistar
5.
Cell Calcium ; 121: 102904, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38728790

ABSTRACT

The smooth muscle-walled blood vessels control blood pressure. The vessel lumen is lined by an endothelial cell (ECs) layer, interconnected to the surrounding smooth muscle cells (SMCs) by myoendothelial gap junctions. Gap junctions also maintain homo-cellular ECs-ECs and SMCs-SMCs connections. This gap junction network nearly equalises both cells' membrane potential and cytosolic ionic composition, whether in resting or stimulated conditions. When acetylcholine (ACh) activates ECs M3 receptors, a complex signalling cascade involving second messengers and ion channels is triggered to induce vasodilation.


Subject(s)
Acetylcholine , Arachidonic Acid , Endothelium, Vascular , Gap Junctions , Vasodilation , Vasodilation/drug effects , Arachidonic Acid/metabolism , Humans , Gap Junctions/metabolism , Animals , Acetylcholine/metabolism , Acetylcholine/pharmacology , Endothelium, Vascular/metabolism , Ion Channels/metabolism , Endothelial Cells/metabolism , Myocytes, Smooth Muscle/metabolism , Receptor, Muscarinic M3/metabolism , Muscle, Smooth, Vascular/metabolism , Signal Transduction
6.
Exp Gerontol ; 192: 112457, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38728795

ABSTRACT

BACKGROUND: Endothelial function declines with age and plays a critical role in cardiovascular health. Therefore, investigating endothelial function in successful aging models, such as centenarians, is of interest. Flow-mediated dilation (FMD) of the brachial artery is the gold standard for measuring endothelial function in vivo in humans. Therefore, we investigated, for the first time, the FMD of the brachial artery in a group of healthy centenarians. METHODS: Selected as part of the ABCD project (nutrition, cardiovascular wellness, and diabetes) centenarians (aged ≥100 years) living in the municipalities of Madonie (Palermo, Italy) were compared with a younger (aged <65 years) sex-matched control group from the ABCD general cohort. FMD of the brachial artery was measured in all participants using a real-time computed video analysis system for B-mode ultrasound images. Body composition (bioimpedance), carotid intima-media thickness (IMT), and ankle-brachial index (ABI) were also measured. RESULTS: Eleven participants (males 36.4 %; age: 101 ± 1 years) out of 28 healthy centenarians successfully cooperated with the FMD test procedures, which require remaining with the upper limb immobile for approximately 10 min. This subgroup was compared with a control group of 76 healthy and younger individuals (males 36.8 %; aged: 41 ± 14 years; P < 0.001). Centenarians exhibited better endothelial function than the control group (FMD: 12.1 ± 4.3 vs 8.6 ± 5.3 %; P < 0.05). The carotid IMT was higher in the centenarian group than in the control group (0.89 ± 0.09 vs 0.56 ± 0.18 mm; P < 0.001), whereas the ABI was comparable between the two groups. CONCLUSIONS: This small group of centenarians demonstrated an unusually favorable endothelial function, which may contribute to their unique aging profile. Further research is needed to determine whether FMD is a valid prognostic marker for successful aging.


Subject(s)
Ankle Brachial Index , Brachial Artery , Carotid Intima-Media Thickness , Endothelium, Vascular , Vasodilation , Humans , Male , Female , Brachial Artery/physiology , Endothelium, Vascular/physiology , Italy , Aged, 80 and over , Vasodilation/physiology , Body Composition/physiology , Aged , Case-Control Studies , Middle Aged , Aging/physiology , Healthy Aging/physiology
7.
Placenta ; 152: 65-71, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38810530

ABSTRACT

INTRODUCTION: Citral is a low-toxicity monoterpene that has a vasodilator effect on various smooth muscles, and The present study aimed to evaluate its vasorelaxant effect on umbilical vessels of normotensive parturients (NTP) and with preeclampsia parturients (PEP). METHOD: Segments of human umbilical artery (HUA) and vein (HUV) of NTP or PEP were mounted in a bath to record the force of contraction, under tension of 3.0 gf and contracted with the contracting agents: K+ (60 mM), 5 -HT (10 µM) and Ba2+ (1-30 mM). Next, the effect of citral (1-3000 µM) on these contractions and on basal tone was evaluated. RESULTS: In HUA and HUV, citral (1-1000 µM), in NTP condition, inhibited contractions evoked by K+ (IC50 of 413.5 and 271.3, respectively) and by 5-HT (IC50 of 164.8 and 574.3). In the PEP condition, in HUA and HUV, citral also inhibited the contractions evoked by K+ (IC50 of 363.3 and 218.3, respectively) and 5-HT (IC50 of 432.1 and 520.4). At a concentration of 1000 µM, citral completely or almost completely (>90 %) inhibited all contractions. At a concentration of 100-1000 µM, citral, in general, was already able to reduce the contraction induced by 1-3 mM Ba2+ in both AUH and VUH, under NTP and PEP conditions. DISCUSSION: Citral has been shown to be an effective HUA and HUV vasodilator in NTP and PEP. As its toxicity is low, it suggests that this substance can be considered a potential therapeutic agent.


Subject(s)
Acyclic Monoterpenes , Monoterpenes , Pre-Eclampsia , Umbilical Arteries , Vasodilator Agents , Humans , Female , Pregnancy , Pre-Eclampsia/physiopathology , Acyclic Monoterpenes/pharmacology , Monoterpenes/pharmacology , Umbilical Arteries/drug effects , Adult , Vasodilator Agents/pharmacology , Umbilical Veins/drug effects , Vasodilation/drug effects
8.
J Appl Physiol (1985) ; 136(6): 1526-1545, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38695358

ABSTRACT

Intrauterine growth restriction (IUGR) is a common complication of pregnancy. We previously demonstrated that IUGR is associated with an impaired nitric oxide (NO)-induced relaxation in the human umbilical vein (HUV) of growth-restricted females compared to appropriate for gestational age (AGA) newborns. We found that phosphodiesterase (PDE) inhibition improved NO-induced relaxation in HUV, suggesting that PDEs could represent promising targets for therapeutic intervention. This study aimed to investigate the effects of PDE inhibition on human umbilical arteries (HUAs) compared to HUV. Umbilical vessels were collected in IUGR and AGA term newborns. NO-induced relaxation was studied using isolated vessel tension experiments in the presence or absence of the nonspecific PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX). PDE1B, PDE1C, PDE3A, PDE4B, and PDE5A were investigated by Western blot. NO-induced vasodilation was similar between IUGR and AGA HUAs. In HUAs precontracted with serotonin, IBMX enhanced NO-induced relaxation only in IUGR females, whereas in HUV IBMX increased NO-induced relaxation in all groups except IUGR males. In umbilical vessels preconstricted with the thromboxane A2 analog U46619, IBMX improved NO-induced relaxation in all groups to a greater extent in HUV than HUAs. However, the PDE protein content was higher in HUAs than HUV in all study groups. Therefore, the effects of PDE inhibition depend on the presence of IUGR, fetal sex, vessel type, and vasoconstrictors implicated. Despite a higher PDE protein content, HUAs are less sensitive to IBMX than HUV, which could lead to adverse effects of PDE inhibition in vivo by impairment of the fetoplacental hemodynamics.NEW & NOTEWORTHY The effects of phosphodiesterase inhibition on the umbilical circulation depend on the presence of intrauterine growth restriction, the fetal sex, vessel type, and vasoconstrictors implicated. The human umbilical vascular tone regulation is complex and depends on the amount and activity of specific proteins but also probably on the subcellular organization mediating protein interactions. Therefore, therapeutic interventions using phosphodiesterase inhibitors to improve the placental-fetal circulation should consider fetal sex and both umbilical vein and artery reactivity.


Subject(s)
Fetal Growth Retardation , Nitric Oxide , Phosphodiesterase Inhibitors , Umbilical Arteries , Umbilical Veins , Vasodilation , Humans , Female , Umbilical Arteries/drug effects , Male , Vasodilation/drug effects , Vasodilation/physiology , Umbilical Veins/drug effects , Phosphodiesterase Inhibitors/pharmacology , Fetal Growth Retardation/drug therapy , Fetal Growth Retardation/physiopathology , Nitric Oxide/metabolism , Pregnancy , Infant, Newborn , Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism , 1-Methyl-3-isobutylxanthine/pharmacology , Sex Factors , Phosphoric Diester Hydrolases/metabolism
9.
Am J Physiol Heart Circ Physiol ; 327(1): H118-H130, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38758130

ABSTRACT

One of the initiating events in preeclampsia (PE) is placental ischemia. Rodent models of placental ischemia do not present with vascular endothelial dysfunction, a hallmark of PE. We previously demonstrated a role for leptin in endothelial dysfunction in pregnancy in the absence of placental ischemia. We hypothesized that placental ischemia requires hyperleptinemia and endothelial mineralocorticoid receptor (ECMR) expression to induce PE-associated endothelial dysfunction in pregnant mice. We induced placental ischemia via the reduced uterine perfusion pressure (RUPP) procedure in pregnant ECMR-intact (ECMR+/+) and ECMR deletion (ECMR-/-) mice at gestational day (GD) 13. ECMR+/+ RUPP pregnant mice also received concurrent leptin infusion via miniosmotic pump (0.9 mg/kg/day). RUPP increased blood pressure via radiotelemetry and decreased fetal growth in ECMR+/+ pregnant mice. Both increases in blood pressure and reduced fetal growth were abolished in RUPP ECMR-/- mice. Placental ischemia did not decrease endothelial-dependent relaxation to acetylcholine (ACh) but increased phenylephrine (Phe) contraction in mesenteric arteries of pregnant mice, which was ablated by ECMR deletion. Addition of leptin to RUPP mice significantly reduced ACh relaxation in ECMR+/+ pregnant mice, accompanied by an increase in soluble FMS-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PLGF) ratio. In conclusion, our data indicate that high leptin levels drive endothelial dysfunction in PE and that ECMR is required for clinical characteristics of hypertension and fetal growth restriction in placental ischemia PE. Collectively, we show that both ECMR and leptin play a role to mediate PE.NEW & NOTEWORTHY Leptin is a key feature of preeclampsia that initiates vascular endothelial dysfunction in preeclampsia characterized by placental ischemia. Endothelial mineralocorticoid receptor (ECMR) deletion in placental ischemia protects pregnant mice from elevations in blood pressure and fetal growth restriction in pregnancy. Increases in leptin production mediate the key pathological feature of endothelial dysfunction in preeclampsia in rodents. ECMR activation contributes to the increase in blood pressure and fetal growth restriction in preeclampsia.


Subject(s)
Ischemia , Leptin , Placenta , Pre-Eclampsia , Receptors, Mineralocorticoid , Animals , Pregnancy , Female , Leptin/metabolism , Leptin/blood , Placenta/metabolism , Placenta/blood supply , Ischemia/physiopathology , Ischemia/metabolism , Ischemia/genetics , Receptors, Mineralocorticoid/metabolism , Receptors, Mineralocorticoid/genetics , Pre-Eclampsia/metabolism , Pre-Eclampsia/physiopathology , Pre-Eclampsia/genetics , Mice, Knockout , Blood Pressure , Mice, Inbred C57BL , Mice , Disease Models, Animal , Fetal Growth Retardation/metabolism , Fetal Growth Retardation/physiopathology , Fetal Growth Retardation/genetics , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Vasodilation/drug effects
10.
Eur J Pharmacol ; 975: 176636, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38729417

ABSTRACT

Endothelial cells express multiple receptors mediating estrogen responses; including the G protein-coupled estrogen receptor (GPER). Past studies on nitric oxide (NO) production elicited by estrogens raised the question whether 17-ß-estradiol (E2) and natural phytoestrogens activate equivalent mechanisms. We hypothesized that E2 and phytoestrogens elicit NO production via coupling to distinct intracellular pathways signalling. To this aim, perfusion of E2 and phytoestrogens to the precontracted rat mesentery bed examined vasorelaxation, while fluorescence microscopy on primary endothelial cells cultures quantified single cell NO production determined following 4-amino-5-methylamino-2',7'-difluoroescein diacetate (DAF) incubation. Daidzein (DAI) and genistein (GEN) induced rapid vasodilatation associated to NO production. Multiple estrogen receptor activity was inferred based on the reduction of DAF-NO signals; G-36 (GPER antagonist) reduced 75 % of all estrogen responses, while fulvestrant (selective nuclear receptor antagonist) reduced significantly more the phytoestrogens responses than E2. The joint application of both antagonists abolished the E2 response but not the phytoestrogen-induced DAF-NO signals. Wortmannin or LY-294002 (PI3K inhibitors), reduced by 90% the E2-evoked signal while altering significantly less the DAI-induced response. In contrast, H-89 (PKA inhibitor), elicited a 23% reduction of the E2-induced signal while blocking 80% of the DAI-induced response. Desmethylxestospongin-B (IP3 receptor antagonist), decreased to equal extent the E2 or the DAI-induced signal. Epidermal growth factor (EGF) induced NO production, cell treatment with AG-1478, an EGF receptor kinase inhibitor reduced 90% DAI-induced response while only 53% the E2-induced signals; highlighting GPER induced EGF receptor trans-modulation. Receptor functional selectivity may explain distinct signalling pathways mediated by E2 and phytoestrogens.


Subject(s)
Cyclic AMP-Dependent Protein Kinases , ErbB Receptors , Estradiol , Nitric Oxide , Phosphatidylinositol 3-Kinases , Phytoestrogens , Signal Transduction , Vasodilation , Animals , Phytoestrogens/pharmacology , Estradiol/pharmacology , Nitric Oxide/metabolism , Rats , Signal Transduction/drug effects , Vasodilation/drug effects , Cyclic AMP-Dependent Protein Kinases/metabolism , Phosphatidylinositol 3-Kinases/metabolism , ErbB Receptors/metabolism , Male , Isoflavones/pharmacology , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Genistein/pharmacology , Receptors, Estrogen/metabolism , Rats, Wistar
11.
J Mol Cell Cardiol ; 192: 94-108, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38754551

ABSTRACT

While exercise-mediated vasoregulation in the myocardium is understood to be governed by autonomic, myogenic, and metabolic-mediated mechanisms, we do not yet understand the spatial heterogeneity of vasodilation or its effects on microvascular flow patterns and oxygen delivery. This study uses a simulation and modeling approach to explore the mechanisms underlying the recruitment of myocardial perfusion and oxygen delivery in exercise. The simulation approach integrates model components representing: whole-body cardiovascular hemodynamics, cardiac mechanics and myocardial work; myocardial perfusion; and myocardial oxygen transport. Integrating these systems together, model simulations reveal: (1.) To match expected flow and transmural flow ratios at increasing levels of exercise, a greater degree of vasodilation must occur in the subendocardium compared to the subepicardium. (2.) Oxygen extraction and venous oxygenation are predicted to substantially decrease with increasing exercise level preferentially in the subendocardium, suggesting that an oxygen-dependent error signal driving metabolic mediated recruitment of flow would be operative only in the subendocardium. (3.) Under baseline physiological conditions approximately 4% of the oxygen delivered to the subendocardium may be supplied via retrograde flow from coronary veins.


Subject(s)
Computer Simulation , Coronary Circulation , Exercise , Models, Cardiovascular , Myocardium , Oxygen , Exercise/physiology , Humans , Oxygen/metabolism , Myocardium/metabolism , Hemodynamics , Oxygen Consumption , Heart/physiology , Vasodilation
12.
Arq Bras Cardiol ; 121(4): e20230236, 2024 Apr.
Article in Portuguese, English | MEDLINE | ID: mdl-38695407

ABSTRACT

BACKGROUND: Vascular dysfunction constitutes the etiology of many diseases, such as myocardial infarction and hypertension, with the disruption of redox homeostasis playing a role in the imbalance of the vasomotor control mechanism. Our group previously has shown that thyroid hormones exert protective effects on the aortic tissue of infarcted rats by improving angiogenesis signaling. OBJECTIVE: Investigate the role of triiodothyronine (T3) on vascular response, exploring its effects on isolated aortas and whether there is an involvement of vascular redox mechanisms. METHODS: Isolated aortic rings (intact- and denuded-endothelium) precontracted with phenylephrine were incubated with T3 (10-8, 10-7, 10-6, 10-5, and 10-4 M), and tension was recorded using a force-displacement transducer coupled with an acquisition system. To assess the involvement of oxidative stress, aortic rings were preincubated with T3 and subsequently submitted to an in vitro reactive oxygen species (ROS) generation system. The level of significance adopted in the statistical analysis was 5%. RESULTS: T3 (10-4 M) promoted vasorelaxation of phenylephrine precontracted aortic rings in both intact- and denuded-endothelium conditions. Aortic rings preincubated in the presence of T3 (10-4 M) also showed decreased vasoconstriction elicited by phenylephrine (1 µM) in intact-endothelium preparations. Moreover, T3 (10-4 M) vasorelaxation effect persisted in aortic rings preincubated with NG-nitro-L-arginine methylester (L-NAME, 10 µM), a nonspecific NO synthase (NOS) inhibitor. Finally, T3 (10-4 M) exhibited, in vitro, an antioxidant role by reducing NADPH oxidase activity and increasing SOD activity in the aorta's homogenates. CONCLUSION: T3 exerts dependent- and independent-endothelium vasodilation effects, which may be related to its role in maintaining redox homeostasis.


FUNDAMENTO: A disfunção vascular constitui a etiologia de diversas doenças, incluindo infarto do miocárdio e hipertensão, diante da ruptura da homeostase oxi-redutiva ("redox"), desempenhando um papel no desequilíbrio do mecanismo de controle vasomotor. Nosso grupo demonstrou anteriormente que os hormônios tireoidianos melhoram a sinalização da angiogênese, exercendo efeitos protetores sobre o tecido aórtico de ratos infartados. OBJETIVOS: Investigar o papel da triiodotironina (T3) na resposta vascular, explorando seus efeitos em aortas isoladas e a presença de mecanismos redox vasculares. MÉTODOS: Anéis aórticos isolados (endotélio intacto e desnudado) pré-contraídos com fenilefrina foram incubados com T3 (10-8, 10-7, 10-6, 10-5 e 10-4 M) e a tensão foi registrada usando um transdutor de deslocamento de força acoplado a um sistema de coleta. Para avaliar o envolvimento do estresse oxidativo, os anéis aórticos foram pré-incubados com T3 e posteriormente submetidos a um sistema de geração de espécies reativas de oxigênio (ROS) in vitro. O nível de significância adotado na análise estatística foi de 5%. RESULTADOS: A T3 (10-4 M) promoveu o vasorrelaxamento dos anéis aórticos pré-contraídos com fenilefrina em endotélio intacto e desnudado. Os anéis aórticos pré-incubados na presença de T3 (10-4 M) também mostraram diminuição da vasoconstrição provocada pela fenilefrina (1 µM) em preparações de endotélio intacto. Além disso, o efeito vasorrelaxante da T3 (10-4 M) persistiu em anéis aórticos pré-incubados com éster metílico de NG-nitro-L-arginina (L-NAME, 10 µM), um inibidor inespecífico da NO sintase (NOS). Por fim, a T3 (10-4 M) exibiu, in vitro, um papel antioxidante ao reduzir a atividade da NADPH oxidase e aumentar a atividade da SOD nos homogenatos aórticos. CONCLUSÃO: A T3 exerce efeitos dependentes e independentes de endotélio, o que pode estar relacionado ao seu papel na manutenção da homeostase redox.


Subject(s)
Oxidation-Reduction , Oxidative Stress , Rats, Wistar , Reactive Oxygen Species , Triiodothyronine , Vasodilation , Animals , Vasodilation/drug effects , Vasodilation/physiology , Male , Triiodothyronine/pharmacology , Oxidation-Reduction/drug effects , Reactive Oxygen Species/metabolism , Oxidative Stress/drug effects , Phenylephrine/pharmacology , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , Rats , Reproducibility of Results , Vasoconstrictor Agents/pharmacology , Aorta, Thoracic/drug effects , Aorta, Thoracic/physiology , In Vitro Techniques , Vasoconstriction/drug effects , Vasoconstriction/physiology
13.
High Blood Press Cardiovasc Prev ; 31(3): 289-297, 2024 May.
Article in English | MEDLINE | ID: mdl-38739257

ABSTRACT

INTRODUCTION: Prevalence of cardiac and vascular fibrosis in patients with Idiopathic Pulmonary Fibrosis (IPF) has not been extensively evaluated. AIM: In this study, we aimed to evaluate the heart and vessels functional and structural properties in patients with IPF compared to healthy controls. An exploratory analysis regarding disease severity in IPF patients has been done. METHODS: We enrolled 50 patients with IPF (at disease diagnosis before antifibrotic therapy initiation) and 50 controls matched for age and gender. Heart was evaluated through echocardiography and plasmatic NT-pro-brain natriuretic peptide that, together with patients' symptoms, allow to define the presence of Heart Failure (HF) and diastolic dysfunction. Vessels were evaluated through Flow Mediated Dilation (FMD - endothelial function) and Pulse Wave Velocity (PWV-arterial stiffness) RESULTS: Patients with IPF had a prevalence of diastolic disfunction of 83.8%, HF of 37.8% and vascular fibrosis of 76.6%. No statistically significant difference was observed in comparison to the control group who showed prevalence of diastolic disfunction, HF and vascular fibrosis of 67.3%, 24.5% and 84.8%, respectively. Disease severity seems not to affect PWV, FMD, diastolic dysfunction and HF. CONCLUSIONS: Patients with IPF early in the disease course do not present a significant CV fibrotic involvement when compared with age- and sex-matched controls. Bigger and adequately powered studies are needed to confirm our preliminary data and longitudinal studies are required in order to understand the time of appearance and progression rate of heart and vascular involvement in IPF subjects.


Subject(s)
Biomarkers , Idiopathic Pulmonary Fibrosis , Natriuretic Peptide, Brain , Peptide Fragments , Pulse Wave Analysis , Severity of Illness Index , Vascular Stiffness , Humans , Idiopathic Pulmonary Fibrosis/physiopathology , Idiopathic Pulmonary Fibrosis/diagnosis , Female , Male , Aged , Case-Control Studies , Middle Aged , Biomarkers/blood , Prevalence , Peptide Fragments/blood , Natriuretic Peptide, Brain/blood , Heart Failure/physiopathology , Heart Failure/diagnosis , Ventricular Function, Left , Fibrosis , Predictive Value of Tests , Vasodilation , Risk Factors
14.
J Clin Hypertens (Greenwich) ; 26(6): 599-614, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38708922

ABSTRACT

Endothelial dysfunction is crucial factor to the hypertension occurrence, and controversy remains regarding the effect of exercise on improving endothelial function in hypertensive patients. The authors used meta-analysis to evaluate the intervention effect of exercise on endothelial function in hypertensive patients and to investigate exercise protocols that may have a greater intervention effect. A total of 37 studies and a total of 2801 participants were included. The results were as follows: endogenous nitric oxide (NO)[SMD = .89, 95% CI (.48, 1.30), p < .0001], endothelin-1 (ET-1): [SMD = -.94, 95% CI (-1.15, -.73), p <. 0001], flow-mediated dilation (FMD) [SMD = -.57, 95% CI (.36, .79), p < .000001]. In subgroup analysis, high-intensity aerobic exercise, with a single exercise duration of 35-50 min, 3-4 times/week for a total of 10-12 weeks, had the largest amount of intervention effect on NO, and moderate-intensity resistance exercise, with a single exercise duration of ≥60 min, 6 times/week for a total of 15-18 weeks, had the largest amount of intervention effect on ET-1. In conclusion, exercise can improve NO levels, FDM levels, and reduce ET-1 secretion of hypertension patients, thereby improve their endothelial function. The ideal intervention effect of improving NO level was more likely to be obtained by taking the exercise prescription of high-intensity aerobic exercise with a single exercise duration of 35-50 min, 3-4 times/week for 10-12 weeks; the ideal intervention effect of improving ET-1 was more likely to be obtained by taking the exercise prescription of oderate -intensity resistance exercise with a single exercise duration of ≥60 min, 6 times/week for 15-18 weeks.


Subject(s)
Endothelin-1 , Endothelium, Vascular , Exercise Therapy , Hypertension , Nitric Oxide , Humans , Hypertension/therapy , Hypertension/physiopathology , Endothelium, Vascular/physiopathology , Endothelium, Vascular/physiology , Endothelin-1/blood , Endothelin-1/metabolism , Nitric Oxide/metabolism , Exercise Therapy/methods , Exercise/physiology , Vasodilation/physiology , Male , Female , Middle Aged , Aged , Adult
15.
J Am Heart Assoc ; 13(9): e032698, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38690710

ABSTRACT

BACKGROUND: Provoked anger is associated with an increased risk of cardiovascular disease events. The underlying mechanism linking provoked anger as well as other core negative emotions including anxiety and sadness to cardiovascular disease remain unknown. The study objective was to examine the acute effects of provoked anger, and secondarily, anxiety and sadness on endothelial cell health. METHODS AND RESULTS: Apparently healthy adult participants (n=280) were randomized to an 8-minute anger recall task, a depressed mood recall task, an anxiety recall task, or an emotionally neutral condition. Pre-/post-assessments of endothelial health including endothelium-dependent vasodilation (reactive hyperemia index), circulating endothelial cell-derived microparticles (CD62E+, CD31+/CD42-, and CD31+/Annexin V+) and circulating bone marrow-derived endothelial progenitor cells (CD34+/CD133+/kinase insert domain receptor+ endothelial progenitor cells and CD34+/kinase insert domain receptor+ endothelial progenitor cells) were measured. There was a group×time interaction for the anger versus neutral condition on the change in reactive hyperemia index score from baseline to 40 minutes (P=0.007) with a mean±SD change in reactive hyperemia index score of 0.20±0.67 and 0.50±0.60 in the anger and neutral conditions, respectively. For the change in reactive hyperemia index score, the anxiety versus neutral condition group by time interaction approached but did not reach statistical significance (P=0.054), and the sadness versus neutral condition group by time interaction was not statistically significant (P=0.160). There were no consistent statistically significant group×time interactions for the anger, anxiety, and sadness versus neutral condition on endothelial cell-derived microparticles and endothelial progenitor cells from baseline to 40 minutes. CONCLUSIONS: In this randomized controlled experimental study, a brief provocation of anger adversely affected endothelial cell health by impairing endothelium-dependent vasodilation.


Subject(s)
Anger , Anxiety , Endothelium, Vascular , Vasodilation , Humans , Male , Female , Adult , Endothelium, Vascular/physiopathology , Anxiety/psychology , Endothelial Progenitor Cells/metabolism , Middle Aged , Sadness , Cell-Derived Microparticles/metabolism , Hyperemia/physiopathology , Emotions , Young Adult , Time Factors , Endothelial Cells
16.
J Am Heart Assoc ; 13(10): e030497, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38726886

ABSTRACT

BACKGROUND: Abdominal obesity is associated with endothelial dysfunction and poorer vascular health. Avocado consumption improves postprandial endothelial function; however, the longer-term effects remain unclear. It was hypothesized that the daily addition of 1 avocado to a habitual diet for 6 months would improve flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity in individuals with abdominal obesity (waist circumference ≥35 in for women, ≥40 in for men), compared with a habitual diet low in avocados. METHODS AND RESULTS: HAT (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled, parallel-arm study that investigated the health effects of adding 1 avocado per day to a habitual diet in individuals with abdominal obesity. At the Pennsylvania State University, University Park study center (n=134; age, 50 ± 13 years; women, 78%; body mass index, 32.6 ± 4.8 kg/m2), markers of vascular function were measured, including endothelial function, assessed via brachial artery flow-mediated dilation, and arterial stiffness, assessed via carotid-femoral pulse wave velocity. Between-group differences in 6-month change in flow-mediated dilation and carotid-femoral pulse wave velocity were assessed using independent t tests. Prespecified subgroup analyses were conducted using linear regression. No significant between-group differences in flow-mediated dilation (mean difference=-0.62% [95% CI, -1.70 to 0.46]) or carotid-femoral pulse wave velocity (0.25 m/s [95% CI, -0.13 to 0.63]) were observed. Results of the subgroup analyses were consistent with the primary analyses. CONCLUSIONS: Longer-term consumption of 1 avocado per day as part of a habitual diet did not improve measures of vascular function compared with a habitual diet low in avocados in individuals with abdominal obesity. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03528031.


Subject(s)
Endothelium, Vascular , Obesity, Abdominal , Persea , Vascular Stiffness , Vasodilation , Humans , Female , Male , Middle Aged , Obesity, Abdominal/physiopathology , Obesity, Abdominal/diet therapy , Obesity, Abdominal/diagnosis , Vascular Stiffness/physiology , Vasodilation/physiology , Endothelium, Vascular/physiopathology , Adult , Carotid-Femoral Pulse Wave Velocity , Time Factors , Pulse Wave Analysis , Treatment Outcome , Brachial Artery/physiopathology , Diet
17.
J Appl Physiol (1985) ; 136(6): 1488-1495, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38722754

ABSTRACT

Advancing age increases cardiovascular disease risk, in part, because of impaired glycocalyx thickness and endothelial dysfunction. Glycocalyx-targeted therapies, such as Endocalyx Pro, could improve both glycocalyx thickness and endothelial function in older adults; however, this has yet to be tested. We hypothesized that Endocalyx Pro supplementation would increase glycocalyx thickness and endothelial function in older adults. Twenty-three older adults aged 66 ± 7 yr (52% female) were enrolled in a randomized, double-blind, placebo-controlled, parallel-arms study to investigate the effect of 12-wk Endocalyx Pro supplementation (3,712 mg/day) on glycocalyx thickness and endothelial function. Glycocalyx thickness was assessed using the GlycoCheck, and endothelial function was determined via brachial artery flow-mediated dilation (FMD). Between-group comparisons revealed Endocalyx Pro did not increase glycocalyx thickness in microvessels 4-25 µm (P = 0.33), 4-7 µm (P = 0.07), or 10-25 µm (P = 0.47) in diameter when compared with placebo. In addition, Endocalyx Pro did not significantly improve FMD [mean ratio (95%) confidence interval [CI]) for between-group comparisons, 1.16 (0.77-1.74); P = 0.48]. However, Endocalyx Pro improved FMD normalized to shear rate (SR) area under the curve [mean ratio (95% CI) for between-group comparisons, 2.41 (1.14,4.13); P = 0.001]. Moreover, Endocalyx Pro increased capillary glycocalyx thickness more than placebo in individuals not taking antihypertensive medication [mean difference (95% CI) for between-group comparison, -0.08 (-0.15, -0.01); P = 0.02]. Our pilot study suggests that Endocalyx Pro supplementation is feasible in older adults but has no measurable effect on overall glycocalyx thickness and FMD. However, Endocalyx Pro may have select effects on capillary glycocalyx thickness and FMD normalized to shear rate among older adults, but further investigation is warranted.NEW & NOTEWORTHY Endothelial glycocalyx thickness and vascular endothelial function decline with advancing age. Endocalyx Pro is a glycocalyx-targeted therapy that may improve endothelial glycocalyx thickness and vascular endothelial function in older adults. This study demonstrated that 12-wk Endocalyx Pro supplementation did not improve overall endothelial glycocalyx thickness or flow-mediated dilation in older adults; however, Endocalyx Pro did increase capillary glycocalyx thickness in individuals not taking antihypertensive medication and improve flow-mediated dilation normalized to the shear stimulus.


Subject(s)
Brachial Artery , Endothelium, Vascular , Glycocalyx , Humans , Glycocalyx/drug effects , Glycocalyx/metabolism , Female , Male , Aged , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , Endothelium, Vascular/physiopathology , Double-Blind Method , Brachial Artery/drug effects , Brachial Artery/physiology , Brachial Artery/diagnostic imaging , Vasodilation/drug effects , Vasodilation/physiology , Middle Aged , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/physiopathology
18.
Gac Med Mex ; 160(1): 23-31, 2024.
Article in English | MEDLINE | ID: mdl-38753572

ABSTRACT

BACKGROUND: Endothelial dysfunction (ED) suspicion will allow to prevent accelerated atherosclerosis and premature death. OBJECTIVE: To establish the usefulness of thermography for endothelial function screening in adults with cardiovascular risk factors. MATERIAL AND METHODS: Cross-sectional, analytical diagnostic test. A brachial arterial diameter (BAD) increase < 11% at one-minute post-ischemia meant probable ED and was confirmed if BAD was ≥ 11% post-sublingual nitroglycerin. Thermographic photographs of the palmar region were obtained at one minute. Descriptive statistics, ROC curve, Mann-Whitney's U-test, chi-square test, or Fisher's exact test were used. RESULTS: Thirty-eight subjects with a median age of 50 years, and with 624 thermographic measurements were included. Nine had ED (flow-mediated vasodilation [FMV]: 2.5%). The best cutoff point for normal endothelial function in subjects with cardiovascular risk factors was ≥ 36 °C at one minute of ischemia, with 85% sensitivity, 70% specificity, positive and negative predictive values of 78 and 77%, area under the curve of 0.796, LR+ 2.82, LR- 0.22. CONCLUSION: An infrared thermography-measured temperature in the palmar region greater than or equal to 36 °C after one minute of ischemia is practical, non-invasive, and inexpensive for normal endothelial function screening in adults with cardiovascular risk factors.


ANTECEDENTES: La sospecha de disfunción endotelial (DE) permitirá prevenir la aterosclerosis acelerada y la muerte prematura. OBJETIVO: Establecer la utilidad de la termografía en el cribado de la función endotelial en adultos con factores de riesgo cardiovascular. MATERIAL Y MÉTODOS: Estudio transversal analítico de prueba diagnóstica. El incremento del diámetro de la arteria braquial < 11 % a un minuto posisquemia significó probable DE, confirmada si el diámetro fue ≥ 11 % posnitroglicerina sublingual. Se obtuvieron fotografías termográficas al minuto de la región palmar. Se aplicó estadística descriptiva, curva ROC, pruebas U de Mann-Whitney, chi cuadrada o exacta de Fisher. RESULTADOS: Se incluyeron 38 sujetos, mediana de edad de 50 años, con 624 mediciones termográficas; nueve presentaron DE (vasodilatación mediada por flujo de 2.5 %). El mejor punto de corte para la función endotelial normal en sujetos con factores de riesgo cardiovascular fue ≥ 36 °C al minuto de isquemia, con sensibilidad de 85%, especificidad de 70%, valores predictivos positivo y negativo de 78 y 77%, área bajo la curva de 0.796, razón de verisimilitud positiva de 2.82 y razón de verisimilitud negativa de 0.22. CONCLUSIÓN: La medición de la temperatura en la región palmar mediante termografía infrarroja ≥ 36 °C tras un minuto de isquemia es práctica, no invasiva y económica para el cribado de la función endotelial normal en adultos con factores de riesgo cardiovascular.


Subject(s)
Endothelium, Vascular , Thermography , Humans , Thermography/methods , Middle Aged , Male , Female , Cross-Sectional Studies , Endothelium, Vascular/physiopathology , Adult , Aged , Heart Disease Risk Factors , Sensitivity and Specificity , Infrared Rays , Brachial Artery/physiology , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/physiopathology , Vasodilation/physiology , Predictive Value of Tests
19.
JACC Cardiovasc Interv ; 17(9): 1091-1102, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38749588

ABSTRACT

BACKGROUND: Invasive CFT is the gold standard for diagnosing coronary vasomotor dysfunction in patients with ANOCA. Most institutions recommend only testing the left coronary circulation. Therefore, it is unknown whether testing multiple coronary territories would increase diagnostic yield. OBJECTIVES: The aim of this study was to evaluate the diagnostic yield of multivessel, compared with single-vessel, invasive coronary function testing (CFT) in patients with angina and nonobstructive coronary arteries (ANOCA). METHODS: Multivessel CFT was systematically performed in patients with suspected ANOCA. Vasoreactivity testing was performed using acetylcholine provocation in the left (20 to 200 µg) and right (20 to 80µg) coronary arteries. A pressure-temperature sensor guidewire was used for coronary physiology assessment in all three epicardial vessels. RESULTS: This multicenter study included a total of 228 vessels from 80 patients (57.8 ± 11.8 years of age, 60% women). Compared with single-vessel CFT, multivessel testing resulted in more patients diagnosed with coronary vasomotor dysfunction (86.3% vs 68.8%; P = 0.0005), coronary artery spasm (60.0% vs 47.5%; P = 0.004), and CMD (62.5% vs 36.3%; P < 0.001). Coronary artery spasm (n = 48) predominated in the left coronary system (n = 38), though isolated right coronary spasm was noted in 20.8% (n = 10). Coronary microvascular dysfunction (CMD), defined by abnormal index of microcirculatory resistance and/or coronary flow reserve, was present 62.5% of the cohort (n = 50). Among the cohort with CMD, 27 patients (33.8%) had 1-vessel CMD, 15 patients (18.8%) had 2-vessel CMD, and 8 patients (10%) had 3-vessel CMD. CMD was observed at a similar rate in the territories supplied by all 3 major coronary vessels (left anterior descending coronary artery = 36.3%, left circumflex coronary artery = 33.8%, right coronary artery = 31.3%; P = 0.486). CONCLUSIONS: Multivessel CFT resulted in an increased diagnostic yield in patients with ANOCA compared with single-vessel testing. The results of this study suggest that multivessel CFT has a role in the management of patients with ANOCA.


Subject(s)
Acetylcholine , Angina Pectoris , Coronary Artery Disease , Coronary Circulation , Coronary Vasospasm , Coronary Vessels , Predictive Value of Tests , Vasodilator Agents , Humans , Female , Male , Middle Aged , Aged , Coronary Vessels/physiopathology , Coronary Vessels/diagnostic imaging , Vasodilator Agents/administration & dosage , Coronary Vasospasm/physiopathology , Coronary Vasospasm/diagnosis , Acetylcholine/administration & dosage , Angina Pectoris/physiopathology , Angina Pectoris/diagnosis , Angina Pectoris/etiology , Coronary Artery Disease/physiopathology , Coronary Artery Disease/diagnosis , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Cardiac Catheterization , Coronary Angiography , Reproducibility of Results , Vasodilation , Vasoconstriction
20.
Lasers Med Sci ; 39(1): 122, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38703271

ABSTRACT

Pulsed dye lasers are used effectively in the treatment of psoriasis with long remission time and limited side effects. It is, however, not completely understood which biological processes underlie its favorable outcome. Pulsed dye laser treatment at 585-595 nm targets hemoglobin in the blood, inducing local hyperthermia in surrounding blood vessels and adjacent tissues. While the impact of destructive temperatures on blood vessels has been well studied, the effects of lower temperatures on the function of several cell types within the blood vessel wall and its periphery are not known. The aim of our study is to assess the functionality of isolated blood vessels after exposure to moderate hyperthermia (45 to 60°C) by evaluating the function of endothelial cells, smooth muscle cells, and vascular nerves. We measured blood vessel functionality of rat mesenteric arteries (n=19) by measuring vascular contraction and relaxation before and after heating vessels in a wire myograph. To this end, we elicited vascular contraction by addition of either high potassium solution or the thromboxane analogue U46619 to stimulate smooth muscle cells, and electrical field stimulation (EFS) to stimulate nerves. For measurement of endothelium-dependent relaxation, we used methacholine. Each vessel was exposed to one temperature in the range of 45-60°C for 30 seconds and a relative change in functional response after hyperthermia was determined by comparison with the response per stimulus before heating. Non-linear regression was used to fit our dataset to obtain the temperature needed to reduce blood vessel function by 50% (Half maximal effective temperature, ET50). Our findings demonstrate a substantial decrease in relative functional response for all three cell types following exposure to 55°C-60°C. There was no significant difference between the ET50 values of the different cell types, which was between 55.9°C and 56.9°C (P>0.05). Our data show that blood vessel functionality decreases significantly when exposed to temperatures between 55°C-60°C for 30 seconds. The results show functionality of endothelial cells, smooth muscle cells, and vascular nerves is similarly impaired. These results help to understand the biological effects of hyperthermia and may aid in tailoring laser and light strategies for selective photothermolysis that contribute to disease modification of psoriasis after pulsed dye laser treatment.


Subject(s)
Lasers, Dye , Animals , Rats , Male , Lasers, Dye/therapeutic use , Myocytes, Smooth Muscle/physiology , Myocytes, Smooth Muscle/radiation effects , Vasodilation/radiation effects , Vasodilation/physiology , Temperature , Muscle, Smooth, Vascular/radiation effects , Muscle, Smooth, Vascular/physiology , Endothelial Cells/radiation effects , Endothelial Cells/physiology , Vasoconstriction/radiation effects , Vasoconstriction/physiology , Endothelium, Vascular/radiation effects , Rats, Wistar
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