scholarly journals Clopidogrel, independent of the vascular P2Y12 receptor, improves arterial function in small mesenteric arteries from AngII-hypertensive rats

2010 ◽  
Vol 118 (7) ◽  
pp. 463-471 ◽  
Author(s):  
Fernanda R. C. Giachini ◽  
David A. Osmond ◽  
Shali Zhang ◽  
Fernando S. Carneiro ◽  
Victor V. Lima ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Reactivity ◽  
Receptor Activation ◽  
Mesenteric Arteries ◽  
P2y12 Receptor ◽  
Sprague Dawley ◽  
Pharmacological Characterization ◽  
Vascular Responses ◽  
Functional Changes ◽  
Nitric Oxide Bioavailability

The P2Y12 receptor antagonist clopidogrel blocks platelet aggregation, improves systemic endothelial nitric oxide bioavailability and has anti-inflammatory effects. Since P2Y12 receptors have been identified in the vasculature, we hypothesized that clopidogrel ameliorates AngII (angiotensin II)-induced vascular functional changes by blockade of P2Y12 receptors in the vasculature. Male Sprague–Dawley rats were infused with AngII (60 ng/min) or vehicle for 14 days. The animals were treated with clopidogrel (10 mg·kg−1 of body weight·day−1) or vehicle. Vascular reactivity was evaluated in second-order mesenteric arteries. Clopidogrel treatment did not change systolic blood pressure [(mmHg) control-vehicle, 117±7.1 versus control-clopidogrel, 125±4.2; AngII–vehicle, 197±10.7 versus AngII–clopidogrel, 198±5.2], but it normalized increased phenylephrine-induced vascular contractions [(%KCl) vehicle-treated, 182.2±18% versus clopidogrel, 133±14%), as well as impaired vasodilation to acetylcholine [(%) vehicle-treated, 71.7±2.2 versus clopidogrel, 85.3±2.8) in AngII-treated animals. Vascular expression of P2Y12 receptor was determined by Western blot. Pharmacological characterization of vascular P2Y12 was performed with the P2Y12 agonist 2-MeS-ADP [2-(methylthio) adenosine 5′-trihydrogen diphosphate trisodium]. Although 2-MeS-ADP induced endothelium-dependent relaxation [(Emax %)=71±12%) as well as contractile vascular responses (Emax %=83±12%), these actions are not mediated by P2Y12 receptor activation. 2-MeS-ADP produced similar vascular responses in control and AngII rats. These results indicate potential effects of clopidogrel, such as improvement of hypertension-related vascular functional changes that are not associated with direct actions of clopidogrel in the vasculature, supporting the concept that activated platelets contribute to endothelial dysfunction, possibly via impaired nitric oxide bioavailability.

scholarly journals Food Restriction Augmented Alpha1 Adrenergic Mediated Contraction in Mesenteric Arteries

2021 ◽  
Author(s):  
Rany Vorn ◽  
Hae Young Yoo
Keyword(s):  
Nitric Oxide ◽  
Arterial Pressure ◽  
Vascular Function ◽  
Food Restriction ◽  
Vascular Reactivity ◽  
Hypovolemic Shock ◽  
Mesenteric Arteries ◽  
Sprague Dawley ◽  
Underlying Mechanisms ◽  
Endothelial Nitric Oxide

Food restriction (FR) enhances the sensitivity to cardiopulmonary reflexes and alpha1 adrenoreceptors in the female, despite hypotension. The effect of male FR on cardiopulmonary and systemic vascular function is not well understood. This study examines the effects of FR on cardiopulmonary, isolated mesenteric arterial function and potential underlying mechanisms. We hypothesized that FR decreased eNOS activity in mesenteric arteries. Male Sprague Dawley (SD) rats were randomly divided into three groups: (1) control (n=30), (2) 20 percent of food reduction (FR20, n=30), and (3) 40 percent of food reduction (FR40, n=30) for five weeks. Non-invasive blood pressure was measured twice a week. Pulmonary arterial pressure (PAP) was measured using isolated/perfused lungs in rats. The isolated vascular reactivity was assessed in double-wire myograph. After five weeks, food restricted rats exhibited a lower mean arterial pressure and heart rate, however, only FR40 groups exhibited statistically significant differences. The basal tone of PAP and various vasoconstrictors did not show significant differences in pulmonary circulation between each group. We observed that food restriction were enhanced the sensitivity (EC50) in response to α1-adrenoreceptors (phenylephrine, PhE)-induced vasoconstriction, but not to serotonin, U46619, and high K+ in the mesenteric arteries. FR reduced endothelium-dependent relaxation via decreased function of endothelial nitric oxide synthase (eNOS)-nitric oxide (NO) pathway in the mesenteric arteries. PhE-mediated vasoconstriction in mesenteric arteries was eliminated in the presence of eNOS inhibitor (L-NAME). In addition, incubation with NOX2/4 inhibitors (apocynin, GKT137831, VAS2870) and reactive oxygen species (ROS) scavenger inhibitor (Tiron) were eliminated the differences of PhE-mediated vasoconstriction but not to cyclooxygenase inhibitor (indomethacin) in the mesenteric artery. Augmentation of alpha1 adrenergic mediated contraction via inhibition of eNOS-NO pathway by increased activation of ROS through NOX2/4 in response to FR. Reduced eNOS-NO signaling might be a pathophysiological counterbalance to prevent hypovolemic shock in response to FR.

scholarly journals Endothelium-Independent Relaxation of Vascular Smooth Muscle Induced by Persimmon-Derived Polyphenol Phytocomplex in Rats

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 89
Author(s):  
Risa Kudo ◽  
Katsuya Yuui ◽  
Shogo Kasuda
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Mesenteric Arteries ◽  
Inositol Triphosphate ◽  
Sprague Dawley ◽  
Vasorelaxant Effect ◽  
Sprague Dawley Rats ◽  
The Mean ◽  
Artery Disease ◽  
Nitric Oxide Pathway

The vasorelaxant effect of polyphenols is well known, and the mortality rate due to coronary artery disease is low in people who consume polyphenol-containing foods. We aimed to elucidate the mechanism by which polyphenols derived from persimmon juice (PJ) and persimmon leaves (PLs) induce vasorelaxation and suppress vasocontraction in the superior mesenteric arteries isolated from male Sprague Dawley rats. Vasocontraction was induced with 1 µM phenylephrine, and polyphenol-induced vasorelaxation was expressed as a percentage of the previous tone induced by phenylephrine. PJ powder (100 mg/L) induced higher levels of vasorelaxation (mean ± standard error of the mean, 88.6% ± 4.4%) than PLs powder (1 g/L; 72.0% ± 10.8%). Nitric oxide pathway inhibitors (NG-nitro-L-arginine methyl ester + carboxy-PTIO) did not affect persimmon-derived polyphenol-induced vasorelaxation, whereas potassium chloride, tetraethylammonium, and potassium-channel inhibitors did. Vasorelaxation was endothelium independent with both extracts. Phenylephrine-induced vasocontraction was suppressed by pretreatment with PJ and PLs powder, even when inositol triphosphate-mediated Ca2+ release and extracellular Ca2+ influx were inhibited. These results suggest that persimmon-derived polyphenol phytocomplex cause vasorelaxation and inhibit vasocontraction through hyperpolarization of smooth muscle cells. Persimmon-derived polyphenols may be able to prevent cardiovascular diseases caused by abnormal contraction of blood vessels.

Coronary vascular reactivity is improved by endothelin A receptor blockade in DOCA-salt hypertensive rats

1998 ◽  
Vol 274 (6) ◽  
pp. R1613-R1618 ◽  
Author(s):  
Ararat D. Giulumian ◽  
David M. Pollock ◽  
Natalie Clarke ◽  
Leslie C. Fuchs
Keyword(s):  
Vascular Reactivity ◽  
Chronic Treatment ◽  
Vascular Dysfunction ◽  
Mesenteric Arteries ◽  
Intraluminal Pressure ◽  
Receptor Blockade ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Small Arteries ◽  
Salt Hypertension

Endothelin-1 (ET-1) is thought to play an important role in the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Because hypertension is associated with an increased incidence of coronary artery disease, this study was designed to determine if coronary vascular contraction to ET-1 is altered in DOCA-salt hypertensive rats and to determine the effect of chronic treatment of DOCA-salt rats with the selective ETA receptor antagonist A-127722. Male Sprague-Dawley rats were divided into four groups: DOCA, Placebo, DOCA + A-127722, and Placebo + A-127722. A-127722 was administered in drinking water at a concentration of 8 mg/100 ml. After 3 wk, mean arterial pressure (MAP) was significantly enhanced in DOCA-salt compared with Placebo rats. A-127722 significantly inhibited the increase in MAP. Contraction to ET-1 (10−11 to 3 × 10−8 M) was measured in isolated coronary and mesenteric small arteries (200–300 μm, intraluminal diameter) maintained at a constant intraluminal pressure of 40 mmHg and was significantly impaired in vessels from DOCA-salt compared with Placebo rats. Dose-dependent contractions to KCl were also inhibited in coronary, but only minimally impaired in mesenteric, arteries of DOCA-salt rats. Inhibition of nitric oxide synthase activity did not restore contraction to ET-1 in coronary small arteries. However contractions to ET-1 were enhanced in mesenteric small arteries. Chronic treatment with A-127722 significantly restored contraction to ET-1 in coronary, but not in mesenteric, arteries of DOCA-salt rats. Because ETAreceptor blockade impairs the development of hypertension and improves coronary vascular reactivity, these data indicate that ET-1 plays an important role in coronary vascular dysfunction associated with DOCA-salt hypertension.

Chronic iron overload in rats increases vascular reactivity by increasing oxidative stress and reducing nitric oxide bioavailability

Life Sciences ◽  
2015 ◽  
Vol 143 ◽  
pp. 89-97 ◽  
Author(s):  
Vinicius Bermond Marques ◽  
Tatiani Botelho Nascimento ◽  
Rogério Faustino Ribeiro ◽  
Gilson Brás Broseghini-Filho ◽  
Emilly Martinelly Rossi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Iron Overload ◽  
Vascular Reactivity ◽  
Nitric Oxide Bioavailability

scholarly journals Endogenous estrogen mediates vascular reactivity and distensibility in pregnant rat mesenteric arteries

2001 ◽  
Vol 280 (3) ◽  
pp. H956-H961 ◽  
Author(s):  
Yunlong Zhang ◽  
Ken G. Stewart ◽  
Sandra T. Davidge
Keyword(s):  
Vascular Reactivity ◽  
Pressor Response ◽  
Virgin Female ◽  
Mesenteric Arteries ◽  
Female Rats ◽  
Tamoxifen Treatment ◽  
Sprague Dawley ◽  
Arterial Distensibility ◽  
Pregnant Rat ◽  
Endogenous Estrogen

The role of estrogen in the maternal systemic cardiovascular adaptations during pregnancy is still controversial. Female Sprague-Dawley rats were implanted at day 14 of pregnancy with either a 50-mg tamoxifen pellet (estrogen receptor blocker, n = 10) or placebo pellet ( n = 10). Virgin female rats were a nonpregnant control ( n = 7). At days 20–22 of pregnancy, resistance-sized mesenteric arteries were mounted onto a dual-chamber arteriograph system. Pregnancy significantly blunted the pressor response to phenylephrine [measurement of the effective concentration that yielded 50% maximum response (EC50) values were 1.5 ± 0.22 vs. 0.69 ± 0.16 μM ( P < 0.05)] and enhanced vasodilation to ACh [EC50 = 1.13 ± 2.53 vs. 3.13 ± 6.04 nM ( P < 0.05)] compared with nonpregnant rats. However, tamoxifen treatment during pregnancy reversed these effects. Inhibition of nitric oxide (NO) synthase with N G-monomethyl-l-arginine (250 μM) shifted only the responses of the placebo-treated pregnant group to both phenylephrine and ACh. Arterial distensibility in the placebo-treated pregnant group was also significantly increased ( P < 0.05) compared with nonpregnant and tamoxifen-treated pregnant animals. In summary, endogenous estrogen during pregnancy increases NO-dependent modulation of vessel tone and arterial distensibility.

Arginine-nitric oxide pathway and cerebrovascular regulation in cortical spreading depression

1995 ◽  
Vol 269 (1) ◽  
pp. H23-H29 ◽  
Author(s):  
M. Fabricius ◽  
N. Akgoren ◽  
M. Lauritzen
Keyword(s):  
Nitric Oxide ◽  
Cortical Spreading Depression ◽  
Vascular Reactivity ◽  
Spreading Depression ◽  
Clinical Importance ◽  
Receptor Activation ◽  
Marked Rise ◽  
Doppler Flowmetry ◽  
Pial Arterioles ◽  
Cerebrovascular Regulation

Nerve cells release nitric oxide (NO) in response to activation of glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype. We explored the hypothesis that NO influences the changes of cerebral blood flow (CBF) during cortical spreading depression (CSD), which is known to be associated with NMDA receptor activation. CBF was monitored in parietal cortex by laser-Doppler flowmetry in halothane-anesthetized rats. Under control conditions, CSD induced regular changes of CBF, which consisted of four phases: a brief hypoperfusion before the direct current (DC) shift; a marked CBF rise during the DC shift; followed by a smaller, but protracted increase of CBF; and a prolonged CBF reduction (the oligemia). NO synthase inhibition by intravenous and/or topical application of NG-nitro-L-arginine enhanced the brief initial hypoperfusion, but the CBF increases and the oligemia were unchanged. L-Arginine prevented the development of the prolonged oligemia after CSD but had no influence on the marked rise of CBF during CSD. Animals treated with L-arginine recovered the reduced vascular reactivity to hypercapnia after CSD much faster than control rats. Functional denervation of cortical and pial arterioles by tetrodotoxin accentuated the pre-CSD hypoperfusion and the oligemia but did not affect the CBF increases. The results suggest that NO is important for the changes of cerebrovascular regulation following CSD. The observations may have clinical importance, since CBF changes during migraine may be triggered by CSD.

scholarly journals Sex differences in mesenteric endothelial function of streptozotocin-induced diabetic rats: a shift in the relative importance of EDRFs

2012 ◽  
Vol 303 (10) ◽  
pp. H1183-H1198 ◽  
Author(s):  
Rui Zhang ◽  
Der Thor ◽  
Xiaoyuan Han ◽  
Leigh Anderson ◽  
Roshanak Rahimian
Keyword(s):  
Sex Differences ◽  
Vascular Reactivity ◽  
Barium Chloride ◽  
Diabetic Rats ◽  
Mesenteric Arteries ◽  
Female Rat ◽  
Relative Importance ◽  
Atpase Inhibitor ◽  
Male And Female ◽  
Vascular Responses

Several studies suggest that diabetes affects male and female vascular beds differently. However, the mechanisms underlying the interaction of sex and diabetes remain to be investigated. This study investigates whether there are 1) sex differences in the development of abnormal vascular responses and 2) changes in the relative contributions of endothelium-derived relaxing factors in modulating vascular reactivity of mesenteric arteries taken from streptozotocin (STZ)-induced diabetic rats at early and intermediate stages of the disease (1 and 8 wk, respectively). We also investigated the mesenteric expression of the mRNAs for endothelial nitric oxide (NO) synthase (eNOS) and NADPH oxidase (Nox) in STZ-induced diabetes in both sexes. Vascular responses to acetylcholine (ACh) in mesenteric arterial rings precontracted with phenylephrine were measured before and after pretreatment with indomethacin (cyclooxygenase inhibitor), Nω-nitro-l-arginine methyl ester (NOS inhibitor), or barium chloride (Kir blocker) plus ouabain (Na+-K+-ATPase inhibitor). We demonstrated that ACh-induced relaxations were significantly impaired in mesenteric arteries from both male and female diabetic rats at 1 and 8 wk. However, at 8 wk the extent of impairment was significantly greater in diabetic females than diabetic males. Our data also showed that in females, the levels of eNOS, Nox2, and Nox4 mRNA expression and the relative importance of NO to the regulation of vascular reactivity were substantially enhanced, whereas the importance of endothelium-derived hyperpolarizing factor (EDHF) was significantly reduced at both 1 and 8 wk after the induction of diabetes. This study reveals the predisposition of female rat mesenteric arteries to vascular injury after the induction of diabetes may be due to a shift away from a putative EDHF, initially the major vasodilatory factor, toward a greater reliance on NO.

Thrombin-induced vascular reactivity is modulated by ETB receptor-coupled nitric oxide release in rat aorta

1996 ◽  
Vol 271 (3) ◽  
pp. C923-C928 ◽  
Author(s):  
H. I. Magazine ◽  
K. D. Srivastava
Keyword(s):  
Nitric Oxide ◽  
Vascular Tone ◽  
Vascular Reactivity ◽  
Receptor Activation ◽  
Rat Aorta ◽  
Isometric Tension ◽  
Receptor Antagonists ◽  
Receptor Modulation ◽  
No Release ◽  
Etb Receptor

The role of endothelin (ET) receptors in thrombin-induced modulation of vascular tone was evaluated by direct measurement of ET-1 and ET receptor-coupled nitric oxide (NO) release and developed isometric tension in thrombin-treated aortic rings. Here we report that rapid release of ET-1 and subsequent ETB receptor activation are required for production of the potent vasodilator NO by thrombin-stimulated aorta. Thrombin-induced NO release is ablated by pretreatment with ETB receptor antagonists or after ET receptor desensitization by repeated stimulation with ET-1. Thrombin-induced relaxation of precontracted vessels was abrogated in the presence of ETB receptor antagonists and, in contrast, marked contraction to thrombin was observed. These data indicate that the endothelium-dependent vasodilator activity previously attributed to thrombin is indirect and requires ETB receptor-coupled NO release and suggest that ET receptor modulation of thrombin-induced vascular tone may contribute to the increased vasomotor tone observed in diseased and mechanically injured vessels.

Increased systolic blood pressure associated with hypertriglyceridemia in female Sprague-Dawley rats

2019 ◽  
Vol 97 (10) ◽  
pp. 971-979
Author(s):  
Conrad Mogane ◽  
Lebogang P. Mokotedi ◽  
Aletta M.E. Millen ◽  
Frederic S. Michel
Keyword(s):  
Body Mass ◽  
Vascular Reactivity ◽  
Velocity Ratio ◽  
Mesenteric Arteries ◽  
Female Rats ◽  
Cholesterol Concentration ◽  
Diastolic Filling ◽  
Sprague Dawley ◽  
Negatively Associated ◽  
Sprague Dawley Rats

The effect of hyperlipidemia on the cardiovascular system is uncertain in females. The aim of the present study was to determine whether administration of a lipogenic diet alters cardiovascular parameters in female rats. Fifty female Sprague-Dawley rats were assigned into 2 groups of rats receiving a standard or a high-fat, high-sucrose diet (HFHS) for 6 weeks (n = 25 per group). Body mass, blood lipids concentrations, triglycerides clearance, blood pressures (BPs), systolic and diastolic functions, as well as vascular reactivity were assessed at the end of the diet intervention. At termination, body mass was similar between the 2 groups. Fasting blood triglycerides concentration (BTG) was greater in the HFHS group. Triglycerides clearance was impaired in the HFHS group. High-density lipoprotein (HDL) cholesterol concentration was lower in the HFHS group. The early-to-late diastolic filling velocity ratio (E/A) was lower in the HFHS group and negatively associated with BTG. The sensitivity (EC50) of mesenteric arteries to phenylephrine was greater in HFHS and was negatively associated with BTG, but not HDL. Systolic BP was higher in the HFHS group and was positively associated with BTG and HDL. The association between systolic BP and BTG was independent of other lipids measured. In conclusion, hypertriglyceridemia may have increased resistance arteries responsiveness to alpha-agonist and systolic BP in female rats.

scholarly journals Endothelin-1-induced vasoconstriction does not require intracellular Ca2+ waves in arteries from rats exposed to intermittent hypoxia

2014 ◽  
Vol 306 (5) ◽  
pp. H667-H673 ◽  
Author(s):  
Jessica M. Osmond ◽  
Laura V. Gonzalez Bosc ◽  
Benjimen R. Walker ◽  
Nancy L. Kanagy
Keyword(s):  
Sleep Apnea ◽  
Phospholipase C ◽  
Intermittent Hypoxia ◽  
Receptor Activation ◽  
Wave Activity ◽  
Mesenteric Arteries ◽  
Wave Frequency ◽  
Sprague Dawley ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor

Sleep apnea is associated with cardiovascular disease, and patients with sleep apnea have elevated plasma endothelin (ET)-1 concentrations. Rats exposed to intermittent hypoxia (IH), a model of sleep apnea, also have increased plasma ET-1 concentrations and heightened constriction to ET-1 in mesenteric arteries without an increase in global vascular smooth muscle cell Ca2+ concentration ([Ca2+]). Because ET-1 has been shown to increase the occurrence of propagating Ca2+ waves, we hypothesized that ET-1 increases Ca2+ wave activity in mesenteric arteries, rather than global [Ca2+], to mediate enhanced vasoconstriction after IH exposure. Male Sprague-Dawley rats were exposed to sham or IH conditions for 7 h/day for 2 wk. Mesenteric arteries from sham- and IH-exposed rats were isolated, cannulated, and pressurized to 75 mmHg to measure ET-1-induced constriction as well as changes in global [Ca2+] and Ca2+ wave activity. A low concentration of ET-1 (1 nM) elicited similar vasoconstriction and global Ca2+ responses in the two groups. Conversely, ET-1 had no effect on Ca2+ wave activity in arteries from sham rats but significantly increased wave frequency in arteries from IH-exposed rats. The ET-1-induced increase in Ca2+ wave frequency in arteries from IH rats was dependent on phospholipase C and inositol 1,4,5-trisphosphate receptor activation, yet inhibition of phospholipase C and the inositol 1,4,5-trisphosphate receptor did not prevent ET-1-mediated vasoconstriction. These results suggest that although ET-1 elevates Ca2+ wave activity after IH exposure, increases in wave activity are not associated with increased vasoconstriction.

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