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PubMed1998

Estradiol therapy combined with progesterone and endothelium-dependent vasodilation in postmenopausal women.

BACKGROUND: Epidemiological studies indicate that estrogen replacement therapy decreases the risk of cardiovascular events in postmenopausal women. Estrogen may confer cardiovascular protection by improving endothelial function because it increases endothelium-dependent vasodilation. It is not known whether progesterone attenuates the beneficial effects of estrogen on endothelial function. METHODS AND RESULTS: Seventeen postmenopausal women with mild hypercholesterolemia were enrolled in a placebo-controlled, crossover trial to evaluate the effect of transdermal estradiol, with and without vaginal micronized progesterone, on endothelium-dependent vasodilation in a peripheral conduit artery. Brachial artery diameter was measured with high-resolution B-mode ultrasonography. To assess endothelium-dependent vasodilation, brachial artery diameter was determined at baseline and after a flow stimulus induced by reactive hyperemia. To assess endothelium-independent vasodilation, brachial artery diameter was measured after administration of sublingual nitroglycerin. During estradiol therapy, reactive hyperemia caused an 11.1+/-1.0% change in brachial artery diameter compared with 4. 7+/-0.6% during placebo therapy (P<0.001). Progesterone did not significantly attenuate this improvement. During combined estrogen and progesterone therapy, flow-mediated vasodilation of the brachial artery was 9.6+/-0.8% (P=NS versus estradiol alone). Endothelium-independent vasodilation was not altered by estradiol therapy, either with or without progesterone, compared with placebo. There was a modest decrease in total and LDL cholesterol during treatment both with estradiol alone and when estradiol was combined with progesterone (all P<0.001 versus placebo). In a multivariate analysis that included serum estradiol, progesterone, total and LDL cholesterol concentrations, blood pressure, and heart rate, only the estradiol level was a significant predictor of endothelium-dependent vasodilation. CONCLUSIONS: The addition of micronized progesterone does not attenuate the favorable effect of estradiol on endothelium-dependent vasodilation. The vasoprotective effect of hormone replacement therapy may extend beyond its beneficial actions on lipids.

Aged↗

PubMedDate not supplied

Attenuation of cyclic nucleotide-mediated smooth muscle relaxation in blacks as a cause of racial differences in vasodilator function.

BACKGROUND: Vasodilator reactivity is attenuated in normotensive blacks, and this may contribute to their enhanced susceptibility to hypertension and its complications. However, the mechanisms responsible for this phenomenon are unknown. We therefore studied nitric oxide (NO)-dependent and -independent vasorelaxation in healthy blacks and whites to investigate the nature of racial differences in vasodilator function. METHODS AND RESULTS: Forearm flow responses to intra-arterial infusion of increasing doses of acetylcholine (a vasodilator that stimulates endothelial release of NO), sodium nitroprusside (an exogenous NO donor), and isoproterenol (a beta-adrenergic agonist whose vasodilator effect stems from the combination of direct smooth muscle stimulation and endothelial NO release) were studied in 18 normotensive whites and 18 blacks by use of strain-gauge plethysmography. A blunted vasodilator response to acetylcholine (7.2+/-1.1 versus 14.4+/-1.8 mL. min-1. dL-1; P<0.001) and sodium nitroprusside (8.2+/-1.1 versus 12.1+/-1.3 mL. min-1. dL-1; P<0.001) was observed in blacks compared with whites, suggesting decreased cGMP-mediated smooth muscle relaxation. The vasodilator effect of isoproterenol was lower in blacks than in whites both before (10.9+/-1.7 versus 14.9+/-1.5 mL. min-1. dL-1; P=0.006) and after NG-monomethyl-L-arginine (6.1+/-1.2 versus 10. 1+/-0.8 mL. min-1. dL-1; P<0.001), implying that cAMP-dependent vasodilator response to isoproterenol is diminished in blacks. No significant difference was observed in the hyperemic response to forearm ischemia. CONCLUSIONS: Compared with whites, healthy blacks have reduced vasodilation in response to NO-dependent and -independent stimuli. This difference seems to be related to an attenuation in cyclic nucleotide-mediated vascular smooth muscle relaxation and may play a role in the increased prevalence of hypertension and its complications in blacks.

Acetylcholine↗

PubMed1992

Captopril improves impaired endothelium-dependent vasodilation in hypertensive patients.

Animal studies suggest that some angiotensin converting enzyme inhibitors augment endothelium-dependent vasorelaxation. We aimed to determine if captopril augments endothelium-dependent vasodilation in middle-aged hypertensive patients. By using strain-gauge plethysmography, forearm vasodilation evoked with intra-arterial acetylcholine (4, 8, 16, and 24 micrograms/min) or nitroprusside (0.2, 0.4, 0.8, and 1.2 micrograms/min) was examined before and after captopril administration (25 mg per os). Before captopril, forearm vasodilation with acetylcholine was less in hypertensive patients (n = 12) than in age-matched (n = 7) or young (n = 7) normotensive subjects, but forearm vasodilation with nitroprusside did not differ among the three groups. Captopril improved forearm vasodilation in hypertensive patients (n = 7) with acetylcholine but nitroprusside did not. In contrast, nifedipine (10 mg per os) did not alter forearm vasodilation with acetylcholine or nitroprusside in hypertensive patients (n = 5). The decreases in mean blood pressure caused by captopril and nifedipine in hypertensive subjects were comparable. Captopril did not alter forearm vasodilation with acetylcholine or nitroprusside in young normotensive subjects (n = 7). These results suggest that captopril in hypertensive patients may acutely improve impaired endothelium-dependent forearm vasodilation that does not result from reduction in blood pressure per se.

Acetylcholine↗

PubMed1996

Role of nitric oxide, adenosine, and ATP-sensitive potassium channels in insulin-induced vasodilation.

The resistance of various tissues to the vasodilator and metabolic effects of insulin may be an important risk factor in the genesis of hypertension observed in several pathological states. Because of this, it is important to understand the mechanisms by which insulin causes vasodilation. Because insulin is known to raise metabolism, one mechanism by which insulin causes vasodilation could be through metabolic vasodilation. Recently, however, it has been suggested that the insulin-induced vasodilation is mediated by the release of endothelium-derived nitric oxide. Using a model of muscle microcirculation (hamster cremaster), we examined the interactions between insulin, nitric oxide, and tissue metabolism to understand the potential mechanisms by which insulin causes vasodilation. Topical application of insulin (200 microU/mL) to the cremaster resulted in significant increases in arteriolar diameter. Second-order arteriolar diameter increased from 69.6 +/- 6 to 79.8 +/- 5 microns and fourth-order arteriolar diameter from 11.3 +/- 1 to 15.1 +/- 2 microns (n = 8). During nitric oxide synthase inhibition, topical application of insulin caused significant vasodilation in both second- and fourth-order arterioles. In contrast, both adenosine receptor antagonism and blockade of ATP-sensitive potassium channels prevented insulin-induced increases in arteriolar diameter. Our findings suggest a role for increased tissue metabolism, particularly the metabolite adenosine, in mediating insulin-induced vasodilation.

Adenosine↗

PubMed1997

Angiotensin-(1-7) augments bradykinin-induced vasodilation by competing with ACE and releasing nitric oxide.

Recent studies have shown that angiotensin-(1-7) [Ang-(1-7)] interacts with kinins and augments bradykinin (BK)-induced vasodilator responses by an unknown mechanism. In this study, we evaluated whether the potentiation of the BK-induced vasodilation by Ang-(1-7) may be attributable to inhibition of BK metabolism, release of nitric oxide, or both. Isometric tension was measured in intact canine coronary artery rings suspended in organ chambers. 125I-[Tyr0]-BK metabolism was determined in vascular rings by assessing the degradation of the peptide by high-performance liquid chromatography. Ang-(1-7) augmented the vasodilation induced by BK in a concentration-dependent manner in rings preconstricted with the thromboxane analog U46619. The EC50 of BK (2.45 +/- 0.51 nmol/L versus 0.37 +/- 0.08 nmol/L) was shifted leftward by 6.6-fold in the presence of 2 mumol/L concentration of Ang-(1-7). The response was specific for BK. since Ang-(1-7) did not augment the vasodilation induced by either acetylcholine (0.05 mumol/L) or sodium nitroprusside (0.1 mumol/L). Moreover, neither angiotensin I nor angiotensin II (Ang II) duplicated the augmented BK response of Ang-(1-7). Pretreatment of vascular rings with the nitric oxide synthase inhibitor, N omega-nitro-L-arginine (L-NA; 100 mumol/L) completely abolished the effects of Ang-(1-7) on BK-induced vasodilation whereas pretreatment with indomethacin (10 mumol/L) was without effect. The potent specific BK B2 receptor antagonist, Hoe 140. nearly abolished the BK and the Ang-(1-7) potentiated responses at 2 mumol/L, whereas at a lower concentration (20 nmol/L) Hoe 140 shifted the response curve to the right for both Ang-(1-7) and vehicle; however, the augmented response to Ang-(1-7) persisted. Preincubation of vascular rings with 20 mumol/L of the AT1 (CV11974), AT2 (PD123319), or nonselective (Sar1 Thr8-Ang II) receptor antagonists had no significant effect on the Ang-(1-7)-enhanced vasodilator response to BK. Lisinopril (2 mumol/L) significantly enhanced the BK-induced vasodilator response while at the same time it abolished the synergistic action of Ang-(1-7) on BK. In addition, pretreatment with 2 mumol/L Ang-(1-7) significantly inhibited the degradation of 125I-[Tyr0]-BK and the appearance of the BK-(1-7) and BK-(1-5) metabolites in coronary vascular rings. Ang-(1-7) inhibited purified canine angiotensin converting enzyme activity with an IC50 of 0.65 mumol/L. In conclusion. Ang-(1-7) acts as a local synergistic modulator of kinin-induced vasodilation by inhibiting angiotensin converting enzyme and releasing nitric oxide.

Angiotensin I↗

PubMed2000

Transient hypertension directly impairs endothelium-dependent vasodilation of the human microvasculature.

Hypertension is associated with decreased endothelium-dependent vasodilation. However, whether endothelial dysfunction is a cause or a consequence of elevated blood pressure is unknown. Therefore, to determine whether hypertension can directly induce endothelial dysfunction, we investigated the effect of increases in intra-arterial pressure on endothelium-dependent vasodilation of the human microvasculature. Small arteries (internal diameter 202+/-75 micrometer) were isolated from gluteal fat biopsies in 12 healthy normotensive subjects (8 men and 4 women; age, 46+/-10 years). Arteries were cannulated and perfused in chambers oxygenated at 37 degrees C. Endothelium-dependent and -independent responses to acetylcholine (Ach; 10(-9) to 10(-4) mol/L) and sodium nitroprusside (SNP; 10(-9) to 10(-4) mol/L), respectively, were obtained after incubating the vessel with incremental intravascular pressures of 50, 80, and 120 mm Hg for 60 minutes each. The response to Ach was also obtained in different arteries after 3 consecutive incubation periods at 50 mm Hg. Arterial internal diameter was measured directly from amplified digital images. A significant reduction in the vasodilator response to Ach was observed with increases in intravascular pressure (mean vasodilation, 62%, 49%, and 26% at 50, 80, and 120 mm Hg, respectively; P<0.001). In contrast, the response to SNP showed a nonsignificant trend toward greater vasodilation with increases in pressure (mean vasodilation, 40%, 52%, and 57% at 50, 80, and 120 mm Hg, respectively; P=0.10). There was no difference in the consecutive dose-response curves to Ach obtained at the same intravascular pressure (mean vasodilation: 48%, 46%, and 49%; P=0.61). Transient increases in intravascular pressure significantly depress endothelium-dependent vasodilation in human resistance arteries. These findings suggest that elevated blood pressure per se may cause endothelial dysfunction in humans and have implications for the pathophysiology of endothelial dysfunction in hypertension.

Blood Pressure↗

PubMed2001

Epoxyeicosatrienoic acid-mediated renal vasodilation to arachidonic acid is enhanced in SHR.

We tested the hypothesis that cyclooxygenase-independent vasodilation produced by arachidonic acid (AA) is mediated by epoxyeicosatrienoic acids (EETs) and is blunted in the spontaneously hypertensive rat (SHR). At normal perfusion pressure (PP; 70 to 90 mm Hg), AA constricted the renal vasculature in both SHR and normotensive Wistar-Kyoto rats, an effect abolished by cyclooxygenase inhibition, and converted to vasodilation when PP was raised to approximately 200 mm Hg. Unexpectedly, renal vasodilation elicited by AA was greater in the SHR at high PP; for example, 2.5, 5, and 10 microg of AA produced PP declines of 54+/-9, 92+/-10, and 112+/-5 mm Hg, respectively, in SHR compared with 26+/-3, 45+/-5, and 77+/-6 mm Hg in Wistar-Kyoto rats (P:<0.01). However, the renal vasodilator responses to acetylcholine (0.1 microg) and sodium nitroprusside (1 microg) did not differ between strains, indicating that vascular responsiveness to AA was independent of intrinsic changes in vascular smooth muscle. Hyperresponsiveness of the renal vasculature to AA may be unique for the SHR, because it did not occur in Sprague-Dawley rats with angiotensin II-induced hypertension. 5,8,11,14-Eicosatetraynoic acid (ETYA; 4 micromol/L), an inhibitor of all AA pathways, attenuated the vasodilator responses to AA, as did treatment with stannous chloride, which depletes cytochrome P450 enzymes, suggesting that a cytochrome P450 AA metabolite mediated the renal vasodilation. N:-Methylsulfonyl-12,12-dibromododec-11-en-amide (DDMS; 2 micromol/L), a selective omega-hydroxylase inhibitor, did not affect AA-induced vasodilation, whereas selective inhibition of epoxygenases with either miconazole (0.3 micromol/L) or N:-methylsulfonyl-6-(2-propargyloxyphenyl) hexanamide (MS-PPOH; 12 micromol/L) did, indicating that one or more EETs were involved in the renal vasodilator action of AA at high PP. This conclusion was supported by the demonstration that AA greatly enhanced the renal efflux of EETs at high PP but not at basal PP.

5,8,11,14-Eicosatetraynoic Acid↗

PubMed2001

C-type natriuretic peptide-induced vasodilation is dependent on hyperpolarization in human forearm resistance vessels.

Animal studies have demonstrated that CNP causes endothelium-independent vasodilation, which is limited by neutral endopeptidase (NEP) activity. However, the vasodilating mechanism of CNP in humans is still unknown. Therefore, we investigated the vasodilator actions of CNP in human forearm resistance vessels before and after inhibition of nitric oxide (NO) and then prostacyclin production and after inhibition of Ca(2+)-dependent potassium channel activation and NEP activity. Three separate studies were performed. In each study, forearm blood flow was recorded by venous occlusion plethysmography in 8 healthy nonsmoking subjects. Brachial artery infusion of CNP (70, 140, 280, and 560 ng per 100 mL forearm volume per minute) caused significant forearm vasodilation in all studies (forearm blood flow from 3.94 to 8.50 mL per 100 mL forearm volume per minute). Inhibition of the endogenous generation of NO by L-N(G)-monomethyl arginine (by use of the NO-clamp technique) did not block the maximal vasodilating effects of CNP (forearm blood flow from 3.69 to 6.93). In addition, when the cyclooxygenase system was inhibited by 600 mg of acetylsalicylic acid (aspirin) administered orally 30 minutes before start of measurements, the rise in forearm blood flow remained intact (forearm blood flow from 3.31 to 8.27 mL per 100 mL forearm volume per minute). However, inhibition of Ca(2+)-dependent potassium channels with tetraethylammonium chloride (0.1 mg per 100 mL forearm volume per minute) significantly attenuated vasodilation caused by CNP (forearm blood flow from 2.28 to 3.06 mL per 100 mL forearm volume per minute), which suggests that CNP opens vascular potassium channels. Vasodilation to all doses of CNP was significantly increased when activity of NEP was blocked with thiorphan (30 nmol/min), which suggests that NEP activity limits vasodilation of CNP. CNP is a dilator of human resistance vessels that mediates its effects through hyperpolarization of the vessel wall independent of the NO and prostaglandin system. Inhibition of local NEP activity increases CNP bioavailability. This may be of relevance to cardiovascular disease, given that vascular tone is well balanced between NO and an endothelium-derived hyperpolarizing factor, which suggests that in pathological situations, impaired NO activity can be compensated for by enhanced endothelium-derived hyperpolarizing factor release to maintain vascular homeostasis.

Adolescent↗

PubMed1994

Influence of exercise intensity and plasma volume on active cutaneous vasodilation in humans.

The influence of dynamic exercise on active cutaneous vasodilation was evaluated in eight male subjects. We measured the increase in internal body temperature (esophageal temperature, Tes) required to elicit active cutaneous vasodilation and the slope of the linear relationship between increases in forearm skin vascular conductance (delta FVC) and Tes during indirect heating (legs immersed in 44 degrees C water for 30 min), 30 min of light exercise (LEX; 75 +/- 5 W = 30% maximal oxygen uptake, VO2max), and 20 min of moderate exercise (MEX, 149 +/- 7 W = 60% VO2max). Studies were conducted in the supine position at 30 degrees C (RH < 30%) and mean skin temperature averaged 35.09 +/- 0.12 degrees C. During indirect heating and LEX, cutaneous vasodilation occurred after a similar increase in Tes, 0.03 +/- 0.02 degrees C and 0.11 +/- 0.02 degrees C, respectively. During MEX, Tes increased 0.42 +/- 0.06 degrees C before the onset of cutaneous vasodilation (P < 0.05, different from rest and LEX). The relationship between the increase in Tes threshold for vasodilation and exercise intensity was nonlinear, indicating that some minimal exercise intensity was required to elicit a delay in active cutaneous vasodilation. That minimal exercise intensity was greater than 30% VO2max (75 +/- 5 W). During MEX the increase in Tes threshold for vasodilation was inversely related to resting plasma volume (ml.kg-1) with a larger initial plasma volume associated with a smaller increase in Tes threshold for cutaneous vasodilation (r2 = 0.67, P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Echo/Doppler and hemodynamic correlates of vasodilator responsiveness in primary pulmonary hypertension.

To determine correlates of acute vasodilator responsiveness in primary pulmonary hypertension, we retrospectively studied 25 patients, comparing 41 resting echo/Doppler and nine resting catheterization variables with the maximal reduction in pulmonary vascular resistance achieved during vasodilator trials. Twelve vasodilators were tested (mean, 5.6 drugs per patient; range, three to eight). Eight patients were vasodilator responsive, as defined by a reduction in pulmonary vascular resistance greater than or equal to 30 percent in response to at least one agent. Univariate and multivariate analyses revealed only Doppler pulmonic peak flow velocity to be an independent correlate of responsiveness (p less than 0.05). Responders differed from nonresponders in having a higher Doppler pulmonic peak flow velocity (PV) (SD 81 +/- 24 vs 64 +/- 15 cm/s; p = 0.05), lower mean right atrial pressure (RAP) (6 +/- 4 vs 13 +/- 7 mm Hg; p = 0.04), and longer median survival (37 vs 5 months; p = 0.03). Seven of eight responders had RAP less than or equal to 10 mm Hg, and all responders had PV greater than 60 cm/s. Seven of ten patients with both RAP less than or equal to 10 and PV greater than 60 and one of the 15 remaining patients were vasodilator responsive (p less than 0.001). Thus, echo/Doppler and invasive hemodynamic parameters correlate with acute vasodilator responsiveness in primary pulmonary hypertension. Patients with low PV and high RAP values were almost never vasodilator responsive. Doppler pulmonic peak velocity and mean RAP may be useful in identifying patients most likely to respond to acute vasodilator trials and those in whom testing is unlikely to yield positive results.

Adult↗

PubMed2005

Does handgrip exercise training increase forearm ischemic vasodilator responses in patients receiving hemodialysis?

In patients receiving hemodialysis, exercise capacity is extremely limited. Although vasodilation is one of the key phenomena for blood perfusion into working skeletal muscles during exercise, it is not clear whether the vasodilator capacity is increased after physical training in this population. We attempted to clarify whether handgrip exercise training increases forearm vasodilator responses to arterial occlusion, and to determine the relationship between muscle contraction function and the vasodilator responses in patients receiving hemodialysis. Eight patients and 7 age-matched healthy controls were tested. The patients participated in handgrip training four times a week for 6 weeks. Before and after the training the maximum muscle strength and endurance were measured with a handgrip dynamometer, and the forearm vasodilator responses to 3-minute arterial occlusion were measured by the near infrared spectroscopy technique. Maximum strength and endurance were significantly lower in the patients than in the controls. Maximum strength (from 183+/-84 to 228+/-92 Newtons, p<0.05) and endurance (from 19+/-6 to 31+/-8 sec, p<0.05) were both increased after the training in the patients. Vasodilator responses estimated by the ratio of the maximum value of oxyhemoglobin after relief of arterial occlusion to its minimum value before the relief were significantly smaller in the patients compared with those in the controls (132+/-20 vs 161+/-27%, p<0.05). In contrast to the findings in muscle function, the decreased vasodilator responses were not improved after the training (141+/-17%). Additionally, no improvement in the vasodilator responses was observed in the parameters estimated by oxygen saturation. These data suggest that exercise capacity increased by physical training is produced by the functional improvement of skeletal muscles per se, but not by alterations in blood perfusion for oxygenation of the muscles in patients receiving hemodialysis.

Exercise↗

PubMed2006

Impaired coronary endothelium-dependent vasodilation is associated with microalbuminuria in patients with type 2 diabetes and angiographically normal coronary arteries.

OBJECTIVE: Microalbuminuria and impaired endothelium-dependent vasodilation are both predictors for cardiac events in patients with type 2 diabetes. The aim of the study was to evaluate whether microalbuminuria correlated with coronary endothelium-dependent vasodilation. RESEARCH DESIGN AND METHODS: We evaluated 84 patients (47 men, mean age 50.5 +/- 5.9 years) with type 2 diabetes for 9.4 +/- 3.4 years, without angiographic coronary stenosis and without major cardiovascular risk factors or other confounding factors, for endothelium investigation. Quantitative coronary angiography was used to assess coronary artery response to cold pressor testing, used to assess endothelium-dependent vasodilation, and to isosorbide dinitrate (endothelium-independent vasodilation). RESULTS: Endothelium-dependent vasodilation differed in the patients with and without microalbuminuria (changes in coronary artery diameter during cold pressor testing: -15.0 +/- 1.9% vs. -10.2 +/- 1.3%, respectively, P < 0.05) and correlated with urinary albumin excretion rate (r = -0.39, P = 0.003), diastolic blood pressure (r = 0.29, P < 0.01), and left ventricular mass index (r = -0.24, P < 0.05). Independent predictors for endothelium-dependent vasodilation were urinary albumin excretion rate (beta -0.04 [95% CI -0.07 to -0.01], P < 0.005) and left ventricular mass index (-0.26 [-0.49 to -0.05], P < 0.05). Endothelium-independent vasodilation was similar in both groups. CONCLUSIONS: Type 2 diabetic patients with microalbuminuria have a more severely impaired coronary endothelium-dependent vasodilation than those with normoalbuminuria. These data suggest a common pathophysiological process for both coronary vasomotor abnormalities and microalbuminuria.

Albuminuria↗

PubMed1991

Peripheral arterial vasodilation hypothesis of sodium and water retention in pregnancy: implications for pathogenesis of preeclampsia-eclampsia.

Primary peripheral arterial vasodilation with relative underfilling of the arterial circulation occurs in early pregnancy and leads to several consequences, including decreased systolic and diastolic blood pressures, enhanced cardiac output secondary to afterload reduction, stimulation of the renin-angiotensin-aldosterone axis, nonosmotic stimulation of thirst and vasopressin release, and renal sodium and water retention with expansion of the extracellular fluid and plasma volume compartments. These are events known to occur in all states of arterial vasodilation. Pregnancy has, however, several unique features. Primary arterial vasodilation generally is associated with no change or a decrease in renal blood flow and glomerular filtration rate and failure to escape from the sodium-retaining effects of aldosterone. In early pregnancy, renal blood flow and glomerular filtration rate increase by 30-50% in parallel with the peripheral arterial vasodilation but before plasma volume expansion. No known vasodilator exhibits such a profound effect on renal hemodynamics. Vasodilating prostaglandins may contribute to, but cannot explain, this remarkable enhancement of renal hemodynamics in early pregnancy. Therefore, a highly potent, as yet undefined, systemic and renal vasodilator must be unique to pregnancy. The increased glomerular filtration rate and filtered sodium load with enhanced distal tubular sodium delivery allows escape from aldosterone, an effect not observed in other states of arterial underfilling. This vasodilator may also account, at least in part, for the vascular resistance to angiotensin known to occur in normal pregnancy. This hypothesis for the normal physiology of pregnancy sets the stage for understanding the pathogenesis of preeclampsia-eclampsia.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Volume↗

PubMed1980

Mechanism of vasodilation during and after ischemic exercise.

This article reviews work on the cause of the vasodilation associated with exercise in the absence of sufficient blood flow. This situation results in a prolonged period of vasodilation that far exceeds the time required for muscle oxygen consumption (VO2) to return to rest. This prolonged vasodilation is not caused by release of K+ or lactic acid, hyperosmolarity, or lowered vessel wall pO2. The early portion appears to be caused by adenosine release, because tissue adenosine is elevated and theophylline partly blocks the response. The remainder may be caused by prostaglandin release which is elevated late in the post-exercise vasodilation period. Indomethacin reduces the duration of the vasodilation. Histamine may play a role in the vasodilation because tripelennamine reduces it. The vasodilation during the exercise bout is probably the result of at least three factors. K+ release and hyperosmolarity probably help to initiate the vasodilation and adenosine probably becomes the dominant factor after the first 10--20 minutes.

Adenosine↗

PubMed1994

Nitric oxide may participate in V2 vasopressin-receptor-mediated renal vasodilation.

Using pentobarbital-anesthetized euvolemic dogs, we investigated whether vasopressin V2-receptor stimulation induced renal vasodilation and whether nitric oxide (NO) had a role in the process. Intrarenal infusion of arginine-vasopressin (AVP) resulted in renal vasoconstriction with pressor response. After preadministration of a V1-receptor antagonist, however, intrarenal infusion of AVP caused an increase in renal blood flow (RBF) without pressor action, indicating renal vasodilation. This renal vasodilation was not observed when we infused AVP after-simultaneous pretreatment with V1- and V2-receptor antagonists. Even in the absence of the V2-receptor antagonist, this renal vasodilation was attenuated by intrarenal infusion of L-NG-nitroarginine (L-NNA). Concomitant infusion of L-arginine prevented the inhibitory effect of L-NNA on renal vasodilation induced by intrarenal infusion of AVP in the presence of the V1-antagonist. These data indicate that the renal vasodilation caused by intrarenal infusion of AVP in the presence of a V1-antagonist was mediated by V2-receptor stimulation, and the inhibitory effect of L-NNA on V2-receptor-mediated renal vasodilation was attributed to its inhibitory effect on NO synthesis, suggesting that NO may participate in V2-receptor-mediated renal vasodilation.

Animals↗

PubMed1975

Influence of histamine H1- and H2-receptor blockers on sympathetic vasodilator and vasoconstrictor responses in canine paw.

1 Vasodilator responses to histamine, bradykinin and sympathetic nerve stimulation were elicited in the perfused paw of dogs treated with bretylium (15-20 mg/kg) and atropine. The H2-receptor blocking agent, burimamide, when administered in the dose of 5 mg/kg intravenously and 4 mg intra-arterially did not depress significantly these vasodilator responses. The subsequent administration of tripelennamine in the dose of 2.5-5 mg/kg intravenously and 4 mg intra-arterially produced a significant blockade of the response to histamine and reduced the sustained vasodilator response to nerve stimulation. 2 In guanethidine-treated dogs, tripelennamine administered in the same dose following burimamide produced a blockade of the response to histamine comparable to that in the bretylium experiments, but decreased only the sustained vasodilator response to stimulation at 1 Hz. When the order of administration of the antihistamines was reversed in another group of guanethidine-treated dogs, tripelennamine had only a slight blocking effect on the response to histamine and did not affect the responses to nerve stimulation. Burimamide exerted a significant blocking effect on the response to histamine, but not to nerve stimulation. Another H2-receptor blocking agent, metiamide, when given after tripelennamine, also had a marked blocking effect on the response to histamine and almost abolished the vasodilator response to 4-methylhistamine, an H2-agonist. Nevertheless, even in the presence of this profound histamine blockade, the sustained vasodilator response to nerve stimulation remained unchanged. 3 In another group of experiments vasoconstrictor responses to exogenous noradrenaline and sympathetic stimulation were initially depressed by burimamide and later returned to control values. Tripelennamine increased these responses by its uptake blocking action. 4 It is concluded that the sustained vasodilator response is not antagonized by a specific antihistaminic action. The decrease in the sustained vasodilator response produced by antihistamines is produced attributable to potentiation of a residual adrenergic vasoconstricotr effect not completely blocked by bretylium.

Animals↗

PubMed1996

Role of phospholipase C and phospholipase A2 in the nitric oxide-independent vasodilator effect of bradykinin in the rat perfused heart.

The cytochrome P450-dependent component of the coronary vasodilator action of bradykinin which requires activation of K+ channels was examined in terms of the contribution of phospholipases in the rat Langendorff heart preparation. This component was isolated by inhibition of nitric oxide synthase with nitroarginine and cyclooxygenase with indomethacin, neither of which affects the coronary vasodilator action of bradykinin. However, nitroarginine elevated coronary perfusion pressure from approximately 40 to 130 mm Hg. The phospholipase C inhibitor, U73122 {1-(6-((17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl) amino)hexyl)-1H-pyrrole-2,5-dione}, reduced coronary vasodilator responses to bradykinin by greater than 80%. U73122 also diminished the coronary vasodilator action of cromakalim which activates ATP-sensitive K+ channels. The maleimide moiety of U73122 that has the capacity to affect K+ channels inhibited cromakalim-induced coronary vasodilation, but did not affect that to bradykinin. Inhibition of diacylglycerol lipase with RHC 80267 {1,6-bis-(cyclohexyloximinocarbonylamino)-hexane} was without an overall effect on coronary vasodilator responses to bradykinin. The cytosolic phospholipase A2 inhibitor, AACOCF3 {arachidonyl trifluoromethyl ketone¿} decreased responses to bradykinin by up to 90% whereas inhibitors of the secretory form of phospholipase A2 oleyloxyethyl phosphorylcholine and ONO-RS-082 {2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid} were less effective than either AACOCF3 or U73122. The phospholipase inhibitors demonstrated selectivity as they did not affect the coronary vasodilator responses to nitroprusside. We obtained additional evidence for the antiphospholipase activity of the inhibitors by demonstrating their capacity to suppress bradykinin-stimulated increases in the release of prostacyclin, measured as 6-keto prostaglandin F1 alpha. The phospholipase inhibitors did not affect cyclooxygenase activity as the ability of arachidonic acid to stimulate prostaglandin formation was unimpaired. These results indicate that the coronary vasodilator action of bradykinin is linked to the activities of both phospholipase C and A2.

Animals↗

PubMed2006

ACE inhibition restores the vasodilator potency of the endothelium-derived relaxing factor, L-S-nitrosocysteine, in conscious Spontaneously Hypertensive rats.

OBJECTIVE: The major aim of this study was to determine whether the angiotensin converting enzyme (ACE) inhibitors, captopril or enalapril, restore the diminished vasodilator potency of the endothelium-dependent agonist, acetylcholine (ACh), and the endothelium-derived relaxing factor (EDRF), L-S-nitrosocysteine (L-SNC), in conscious Spontaneously Hypertensive (SH) rats. METHODS: The hemodynamic responses elicited by i.v. injections of ACh, L-SNC, and nitric oxide donors such as MAHMA NONOate, were determined in SH rats treated for 7 days with captopril, enalapril, or the direct vasodilator hydralazine. The effects of captopril, enalapril or hydralazine on oxidant stress levels in blood serum and aorta of WKY and SH rats were also determined. RESULTS: Captopril, enalapril and hydralazine elicited equivalent falls in mean arterial pressure and systemic vascular resistances in SH rats. ACh- and L-SNC-induced vasodilation were increased in captopril- or enalapril-treated SH rats such that the responses were equal to those in normotensive Wistar Kyoto rats. The attenuated responses of ACh and L-SNC in SH rats were not improved by hydralazine. The vasodilator effects of MAHMA NONOate, which were substantially augmented in SH rats, were not affected by captopril, enalapril or hydralazine. The levels of oxidant stress were markedly reduced in captopril- or enalapril-treated but not hydralazine-treated SH rats. CONCLUSIONS: The finding that the ACE inhibitors improved the vasodilator potencies of L-SNC and the EDRF released by ACh in SH rats, suggests that the diminished vasodilator potency of these compounds was due to augmented ACE activity, which increased oxidant stress levels. This study provides the first evidence to support the concept that ACE inhibition lowers arterial pressure in SH rats, at least in part, by restoring the vasodilator potency of endothelium-derived L-SNC.

Acetylcholine↗