-
Osaka City Medical Journal Dec 1998We examined the role of endothelium-derived relaxing factor (EDRF) in lidocaine-induced pulmonary vasoconstriction in experiments using the nitric oxide synthase...
We examined the role of endothelium-derived relaxing factor (EDRF) in lidocaine-induced pulmonary vasoconstriction in experiments using the nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NNA) and EDRF precursor L-arginine in a canine cross-circulation model. The left lower lobe of one dog lung was perfused with venous blood from another dog at a constant rate of flow. Pretreatment of ibuprofen was performed to exclude the effects of vasoactive prostanoids. L-NNA significantly inhibited acetylcholine- and bradykinin-induced pulmonary vasodilation without affecting the vasodilatory responses to isoproterenol in pulmonary vessels preconstricted with thromboxane analogue U46619 or prostaglandin F2 alpha. Pulmonary vasoconstriction by 40 micrograms.ml-1 lidocaine infusion after pretreatment with L-NNA was significantly greater than that before pretreatment with L-NNA, and was reversed to the level present without L-NNA treatment by additional administration of L-arginine. We conclude that lidocaine-induced pulmonary vasoconstriction is modulated by the EDRF/NO pathway in dog lung.
Topics: Anesthetics, Local; Animals; Dogs; Lidocaine; Nitric Oxide; Pulmonary Circulation; Vasoconstriction
PubMed: 10097598
DOI: No ID Found -
Current Hypertension Reports Jun 2009Central blood pressure is dependent on the stiffness of large arteries and pulse wave reflection. These parameters are very important in the development of hypertensive... (Review)
Review
Central blood pressure is dependent on the stiffness of large arteries and pulse wave reflection. These parameters are very important in the development of hypertensive target organ disease. Moreover, recent clinical studies have shown their independent predictive value for cardiovascular morbidity and mortality. Therefore, 2007 guidelines for the management of hypertension inserted the evaluation of central arterial stiffness as an important component for assessing total cardiovascular risk. Differences in the way various antihypertensive drugs affect arterial stiffness and central hemodynamics may explain the greater cardio-vascular protection provided by newer drugs (eg, renin-angiotensin system blockers or calcium channel blockers) independent of peripheral blood pressure reduction, as shown by recent clinical studies. However, the predictive value of the attenuation of arterial stiffness, wave reflections, and central blood pressure still needs to be confirmed in prospective, long-term, large-scale therapeutic trials. Thus, whether these measurements should be routinely performed as a diagnostic or therapeutic indicator remains debatable.
Topics: Antihypertensive Agents; Arteries; Blood Pressure; Humans; Hypertension; Treatment Outcome; Vasoconstriction
PubMed: 19442328
DOI: 10.1007/s11906-009-0034-5 -
Journal of Pharmacological Sciences Feb 2004Mechanisms underlying bradykinin-induced vasoconstriction were investigated in rat perfused mesenteric vascular beds with active tone. In preparations with intact... (Comparative Study)
Comparative Study
Mechanisms underlying bradykinin-induced vasoconstriction were investigated in rat perfused mesenteric vascular beds with active tone. In preparations with intact endothelium, bolus injections of bradykinin (1 to 1,000 pmol) dose-dependently produced three-phase vascular effects, which consisted of a first-phase vasodilation followed by a second-phase vasoconstriction and a subsequent third-phase vasodilation; these effects were abolished by FR172357 (bradykinin B(2)-receptor antagonist), but not by des-Arg(9)-[Leu(8)]-bradykinin (bradykinin B(1)-receptor antagonist). In preparations with intact endothelium, indomethacin (cyclooxygenase inhibitor), seratrodast (thromboxane A(2) (TXA(2))-receptor antagonist), ONO-3708 (TXA(2)/prostaglandin H(2) (PGH(2))-receptor antagonist) or ozagrel (TXA(2) synthesis inhibitor) markedly inhibited the bradykinin-induced vasoconstriction. In preparations without endothelium, the bradykinin-induced vasoconstriction was abolished by indomethacin and ONO-3708, while seratrodast and ozagrel had no effect. These results suggest that the endothelium-dependent vasoconstriction of bradykinin is mainly mediated by TXA(2) and that prostanoids other than TXA(2), probably PGH(2), in mesenteric vascular smooth muscle are responsible for bradykinin-induced endothelium-independent vasoconstriction.
Topics: Animals; Bradykinin; Dose-Response Relationship, Drug; Endothelium, Vascular; In Vitro Techniques; Male; Mesenteric Arteries; Perfusion; Prostaglandins; Rats; Rats, Wistar; Vasoconstriction
PubMed: 14978348
DOI: 10.1254/jphs.94.115 -
Poultry Science May 2001Bacterial endotoxins stimulate endothelin-mediated, thromboxane-dependent increases in pulmonary vascular resistance in mammals, and thromboxane has been shown to cause...
Bacterial endotoxins stimulate endothelin-mediated, thromboxane-dependent increases in pulmonary vascular resistance in mammals, and thromboxane has been shown to cause an immediate but transient pulmonary vasoconstriction in broiler chickens. In the present study, i.v. injections of 1 mg endotoxin into anesthetized male broilers caused a pulmonary vasoconstrictive response that was delayed in onset by 15 min and that elevated the pulmonary arterial pressure by 10 mm Hg within 25 min postinjection. Thereafter, pulmonary hemodynamic variables gradually (> or = 15 min) returned toward pre-injection levels, and supplemental injections of 4 mg endotoxin during this recovery period failed to reinitiate pulmonary hypertension. In contrast, injecting the thromboxane A2 mimetic U44069 during the endotoxin recovery period triggered pulmonary vasoconstriction and pulmonary hypertension similar in magnitude to the responses triggered by U44069 before endotoxin had been administered. The time course and magnitude of the pulmonary hemodynamic responses to endotoxin were highly variable among individual broilers, whereas the individual responses to U44069 were more consistent. Unanesthetized broilers resembled anesthetized broilers in the time course, magnitude, and variability of their pulmonary hemodynamic responses to endotoxin. Overall, these observations are consistent with the hypothesis that endotoxin initiates a biochemical cascade, culminating in the delayed onset of pulmonary vasoconstriction and pulmonary hypertension within 20 min postinjection. Subsequently, the pulmonary vasculature remains responsive to large bolus injections of exogenous thromboxane mimetic; however depletion of endogenous vasoconstrictive components of the endotoxin-mediated cascade, a compensatory increase in endogenous vasodilators, or the induction of a transient cellular tolerance to endotoxin prevented fourfold higher doses of endotoxin from reversing the return toward a normal pulmonary vascular tone. Individual differences among broilers in their susceptibility to pulmonary hypertension syndrome (ascites) may be related to innate or acquired variability in their pulmonary vascular responsiveness to vasoactive mediators.
Topics: Animals; Chickens; Endotoxins; Hypertension, Pulmonary; Injections, Intravenous; Male; Poultry Diseases; Prostaglandin Endoperoxides, Synthetic; Pulmonary Circulation; Thromboxane A2; Vascular Resistance; Vasoconstriction
PubMed: 11372717
DOI: 10.1093/ps/80.5.647 -
Critical Care (London, England) 2006In the current issue of Critical Care, Friesenecker and colleagues present a well-designed comparative study on the microvascular effects of arginine vasopressin (AVP)... (Comparative Study)
Comparative Study Review
In the current issue of Critical Care, Friesenecker and colleagues present a well-designed comparative study on the microvascular effects of arginine vasopressin (AVP) and norepinephrine (NE) in a physiological, unanesthetized hamster model. The authors clearly demonstrate that AVP, but not NE, has marked vasoconstrictive effects on large arterioles, whereas the impact on small arterioles is comparable for both vasopressors. However, it remains unclear if these results, per se, reflect a stronger vasopressive potential of AVP versus NE, as macrohemodynamic variables were not different between study groups. Since the authors did not investigate the effects of AVP and NE in vasodilatory shock states, the microcirculatory response in sepsis or systemic inflammatory response syndrome remains inconclusive. The same authors previously reported that AVP infusion in patients suffering from vasodilatory shock carries the risk for ischemic skin lesions. This in turn raises the question whether the quality of vasopressors should be judged by their potency.
Topics: Animals; Arginine Vasopressin; Humans; Norepinephrine; Vasoconstriction
PubMed: 16732898
DOI: 10.1186/cc4942 -
Journal of Cardiovascular Pharmacology Jul 2015Vasoconstriction and hypersensitivity to the vasoconstrictive action of serotonin occurs in the early stage of atherosclerosis. Vascular neural nitric oxide synthase...
BACKGROUND AND OBJECTIVE
Vasoconstriction and hypersensitivity to the vasoconstrictive action of serotonin occurs in the early stage of atherosclerosis. Vascular neural nitric oxide synthase (nNOS) plays an important role in the regulation of vascular tone and is vasoprotective against atherosclerosis. In this study, we intended to investigate the possible role of nNOS in mediating the effect of Chinese medicine Tongxinluo (TXL) to attenuate vasoconstriction induced by the chronic injury in the collared carotid artery.
METHODS
Twenty-four male Wistar Kyoto rats were assigned to 2 treatments (n = 12): vehicle and TXL (400 mg·kg·d). After 2 weeks of treatment, adventitia injury was induced by placing a silicone collar around the left carotid artery for 2 weeks. Blood flow and vascular reactivity to serotonin were determined, and carotid arteries were harvested for morphometry, RT-PCR, and Western blotting analysis. Expression of nNOS and phosphorylated ERK1/2 was also analyzed in primary cultured vascular smooth muscle cells after TXL and/or ERK kinase inhibitor treatment.
RESULTS
Adventitia injury induced by the placement of a silicone collar around the carotid artery for 2 weeks led to chronic vasoconstriction and vascular hypersensitivity to serotonin, which was attenuated by TXL treatment. TXL improved the carotid blood flow and normalized the vascular hypersensitivity to serotonin in collared carotid arteries. The expression of nNOS and phosphorylated ERK1/2 was increased by TXL treatment in both collared carotid artery and vascular smooth muscle cells indicating a possible contribution of ERK1/2 and nNOS signaling to the beneficial effects of TXL. Moreover, we showed that the effect of TXL to increase nNOS expression was mediated by the phosphorylated ERK1/2 since the effect could be abolished by the ERK kinase inhibitor PD98059.
CONCLUSIONS
TXL increases nNOS expression in the collared carotid artery through activation of ERK1/2 signaling, which may have contributed to the attenuation of vasoconstriction induced by the collar-induced adventitia injury.
Topics: Animals; Cells, Cultured; Drugs, Chinese Herbal; Enzyme Activation; Gene Expression Regulation, Enzymologic; MAP Kinase Signaling System; Male; Nitric Oxide Synthase Type I; Rats; Rats, Inbred WKY; Vasoconstriction
PubMed: 26164718
DOI: 10.1097/FJC.0000000000000228 -
Clinical Science (London, England :... Dec 19911. The aim of this study was to examine whether arginine vasopressin modulates the vasoconstricting action of phenylephrine in human forearms. 2. In seven healthy... (Clinical Trial)
Clinical Trial
1. The aim of this study was to examine whether arginine vasopressin modulates the vasoconstricting action of phenylephrine in human forearms. 2. In seven healthy subjects, we determined the percentage increases in forearm vascular resistance evoked by intra-arterial infusion of phenylephrine at graded doses during simultaneous intra-arterial infusion of saline or arginine vasopressin at two doses. Similarly, in another seven subjects, we examined the effects of intra-arterial infusions of saline or angiotensin II on the vasoconstricting action of intra-arterial phenylephrine. 3. Arginine vasopressin and angiotensin II caused small, but insignificant, increases in baseline forearm vascular resistance. Arginine vasopressin at the two doses significantly attenuated the percentage increases in forearm vascular resistance evoked with phenylephrine at graded doses. Angiotensin II did not alter the forearm vascular responses to phenylephrine. 4. Intra-arterial infusion of arginine vasopressin at doses of 0.6 and 1.8 ng/min raised the plasma arginine vasopressin concentration in the venous effluents from 1.6 +/- 0.3 (control) to 4.0 +/- 0.9 and to 16.4 +/- 6.9 pg/ml, respectively. 5. These results suggest that arginine vasopressin at physiological concentrations with a minimal direct effect on resistance arteries attenuates the vasoconstricting action of phenylephrine in human forearms.
Topics: Adolescent; Adult; Angiotensin II; Arginine Vasopressin; Forearm; Humans; Male; Phenylephrine; Plethysmography; Vascular Resistance; Vasoconstriction
PubMed: 1662578
DOI: 10.1042/cs0810733 -
Journal of Applied Physiology... Jul 2017Sex differences in the neurovascular control of blood pressure and vascular resistance have been reported. However, the mechanisms underlying the modulatory influence of...
Sex differences in the neurovascular control of blood pressure and vascular resistance have been reported. However, the mechanisms underlying the modulatory influence of sex have not been fully elucidated. Nitric oxide (NO) has been shown to inhibit sympathetic vasoconstriction in resting and contracting skeletal muscle, and estrogen modulates NO synthase (NOS) expression and NO bioavailability. Therefore NO-mediated inhibition of sympathetic vasoconstriction may be enhanced in females. Thus the purpose of the present study was to investigate the hypothesis that sympathetic vasoconstrictor responsiveness would be blunted and NO-mediated inhibition of sympathetic vasoconstriction would be enhanced in females compared with males. Male (M; = 8) and female (F; = 10) Sprague-Dawley rats were anesthetized and surgically instrumented for measurement of arterial blood pressure and femoral artery blood flow and stimulation of the lumbar sympathetic chain. The percentage change of femoral vascular conductance in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae muscle contraction before (control) and after NOS blockade [-nitro-l-arginine methyl ester (l-NAME), 10 mg/kg iv]. At rest, sympathetic vasoconstrictor responsiveness was augmented ( < 0.05) in female compared with male rats at 2 Hz [F: -33 ± 8% (SD); M: -26 ± 6%] but was not different at 5 Hz (F: -55 ± 7%; M: -47 ± 7%). During muscle contraction, evoked vasoconstriction was similar ( > 0.05) in females and males at 2 Hz (F: -12 ± 5%; M: -13 ± 5%) but was blunted ( < 0.05) in females compared with males at 5 Hz (F: -24 ± 5%; M: -34 ± 8%). l-NAME increased ( < 0.05) sympathetic vasoconstrictor responsiveness in both groups at rest and during contraction. Contraction-mediated inhibition of vasoconstriction (sympatholysis) was enhanced ( < 0.05) in females compared with males; however, sympatholysis was not different ( > 0.05) between males and females in the presence of NOS blockade, indicating that NO-mediated sympatholysis was augmented in female rats. These data suggest that sex modulates sympathetic vascular control in resting and contracting skeletal muscle and that a portion of the enhanced sympatholysis in female rats was NO dependent. Sex differences in the neurovascular regulation of blood pressure and vascular resistance have been documented. However, our understanding of the underlying mechanisms that mediate these differences is incomplete. The present study demonstrates that female rats have an enhanced capacity to inhibit sympathetic vasoconstriction during exercise (sympatholysis) and that NO mediates a portion of the enhanced sympatholysis.
Topics: Adrenergic Fibers; Animals; Female; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Rats; Rats, Sprague-Dawley; Sex Characteristics; Vasoconstriction; Vasoconstrictor Agents
PubMed: 28473610
DOI: 10.1152/japplphysiol.00139.2017 -
Pharmacological Research Jun 2004Endothelial cells control the tone and the growth of the underlying vascular smooth muscle by releasing Nitric Oxide (NO). This introduction summarizes the early... (Review)
Review
Endothelial cells control the tone and the growth of the underlying vascular smooth muscle by releasing Nitric Oxide (NO). This introduction summarizes the early experiments which first suggested and then demonstrated the existence of an alternative pathway, endothelium-dependent hyperpolarization. It reviews why endothelium-derived hyperpolarizing factor (EDHF) is not likely to be either NO or prostacyclin. It sets the stage for the other contributions of this special issue devoted to EDHF that will discuss in depth the current knowledge concerning endothelium-dependent hyperpolarizations.
Topics: Animals; Endothelium, Vascular; Humans; Muscle, Smooth, Vascular; Vasoconstriction; Vasodilation
PubMed: 15026027
DOI: 10.1016/j.phrs.2003.11.015 -
Circulation Dec 1995Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide. Controversy persists regarding the predominant ET receptor that mediates coronary vasoconstriction...
BACKGROUND
Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide. Controversy persists regarding the predominant ET receptor that mediates coronary vasoconstriction at pathophysiological concentrations. The aim of the present study was to test the hypothesis that ET mediates local coronary vasoconstriction via the ET-A receptor at low concentrations of exogenous ET-1 designed to mimic pathophysiological states compared with pharmacological concentrations.
METHODS AND RESULTS
ET-1 (group 1, n = 5) or sarafotoxin, a specific ET-B receptor agonist (group 3, n = 6) (each at 2 ng/kg per minute), was infused into the left circumflex coronary artery in the anesthetized dog. In group 2 dogs (n = 5), the same dose of ET-1 was infused with 4 micrograms/kg per minute of the specific ET-A receptor antagonist FR-139317. In group 4 (n = 5), the same dose of sarafotoxin was infused with 50 micrograms/kg per minute of the specific inhibitor of nitric oxide formation, NG-monomethyl-L-arginine (L-NMMA). No difference in hemodynamics, coronary blood flow (CBF), coronary vascular resistance (CVR), or coronary artery diameter (CAD) was observed at baseline between the groups. In group 1, intracoronary ET-1 significantly decreased CBF and CAD in association with an increase in CVR. The percentage decrease in CBF and CAD in the group that received ET-1 and the ET-A receptor antagonist (group 2) was significantly less than that in the group that received ET-1 alone (group 1) (-12 +/- 3% versus -48 +/- 6% [P < .001] and -4.6 +/- 0.8 versus 1.0 +/- 0.3 [P < .05], respectively). The administration of the ET-A receptor antagonist (group 2) abolished the ET-mediated increase in CVR (7 +/- 5% versus 105 +/- 21%, P < .005). There was no significant effect on CBF, CVR, or CAD in the group receiving sarafotoxin alone (group 3). The administration of L-NMMA and sarafotoxin (group 3). The administration of L-NMMA and sarafotoxin (group 4) resulted in a significant percentage decrease in CBF compared with the group that received sarafotoxin alone (-28 +/- 7% versus -8 +/- 2% [P < .05]).
CONCLUSIONS
The present study demonstrates that low concentrations of exogenous ET-1, which may mimic pathophysiological concentrations, result in coronary vasoconstriction mediated predominantly via the ET-A receptor because such vasoconstriction is significantly attenuated by blockade with FR-139317. The ET-B receptor may have a dual vasoconstrictive and vasodilatory effect.
Topics: Animals; Arginine; Azepines; Coronary Vessels; Dogs; Endothelin Receptor Antagonists; Endothelins; Enzyme Inhibitors; Indoles; Nitric Oxide Synthase; Receptor, Endothelin A; Receptor, Endothelin B; Receptors, Endothelin; Vasoconstriction; Viper Venoms; omega-N-Methylarginine
PubMed: 7586319
DOI: 10.1161/01.cir.92.11.3312