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PubMed1993

Endothelium-dependent contraction produced by acetylcholine and relaxation produced by histamine in monkey basilar arteries.

The present experiments were carried out to investigate endothelium-dependence of the responses to ACh, arachidonic acid and histamine in monkey basilar arteries. As we reported previously (1), ACh (10(-7) M) and arachidonic acid (5 x 10(-7) M) caused endothelium-dependent contraction (EDC) in both monkey and canine basilar arteries. The endothelium-derived contracting factor (EDCF) is probably TXA2, since the EDC was attenuated by a cyclooxygenase inhibitor (aspirin, 5 x 10(-5) M), thromboxane A2 (TXA2) synthetase inhibitors (OKY-046, 10(-5) M; RS-5186, 10(-6) M) and TXA2 antagonists (ONO-3708, 10(-8) M; S-145, 5 x 10(-9) M). Histamine caused endothelium-dependent relaxation (EDR) in monkey basilar arteries and EDC in canine basilar arteries. The EDR in monkey basilar arteries was attenuated by nitric oxide synthetase inhibitor, NG-monomethyl-L-arginine (L-NMMA) in a concentration-dependent manner and the EDC in canine basilar arteries was attenuated by aspirin, TAX2 synthetase inhibitors and TXA2 antagonists. The EDR and EDC were antagonized by tripelennamine (10(-6) M) but not by cimetidine (10(-5) M), indicating that they are mediated by H1-receptors. From these results, we suggest that in the monkey basilar artery, either there are two types of endothelium, an EDCF type for ACh and arachidonic acid and an EDRF type for histamine, or there is single type of endothelium with two types of signalling processes, one for EDC and one for EDR.

Acetylcholine↗
PubMed1994

Effects of 17 beta-estradiol on endothelium-dependent relaxation induced by acetylcholine in female rat aorta.

Estrogens have been postulated to play an important role in modulation of vascular responses to endogenous reactive substances. The effects of chronic in vivo treatment with 17 beta-estradiol on relaxant responses to acetylcholine were investigated in the rat aorta isolated from prepubertal female rats. The selectivity of effects of 17 beta-estradiol on acetylcholine-induced relaxation was evaluated using histamine, another endothelium-dependent relaxant in the rat aorta. 17 beta-Estradiol significantly enhanced endothelium-dependent relaxation induced by acetylcholine, but did not alter the vascular responses to acetylcholine in endothelium-denuded aortic rings isolated from prepubertal female rats. In contrast, 17 beta-estradiol did not change endothelium-dependent relaxation induced by histamine in endothelium-intact aortic rings. The results of the present study demonstrate that 17 beta-estradiol selectively enhances acetylcholine-induced endothelium-dependent relaxation in the rat aorta.

Acetylcholine↗
PubMed1984

Revascularization of skin transplanted into the brain: source of the graft endothelium.

Transplantation of tissues into the brain is becoming a feasible therapeutic approach to some neurological diseases. The fate of the graft vasculature is not well understood. The purpose of the present study was to determine the source of the endothelium in the revascularized skin grafts transplanted into the brain. We hypothesized that if the skin endothelium were replaced by brain endothelium then we should observe in the grafts the following: degenerating endothelium soon after grafting, regenerating endothelium subsequently, a time course for reestablishment of circulation that is consistent with the time required for vessel growth and invasion, and doubling of the vascular basement membrane a few weeks later. We found only a few degenerating endothelial cells soon after transplantation and no evidence of regenerating endothelium or of double layers of basement membrane even after prolonged survival. The vessels within mature grafts had morphological characteristics typical of normal skin vessels. We concluded that when tissue fragments are transplanted to the brain, native graft vessels survive and anastomose with host vessels.

Animals↗
PubMed1991

Endothelium-dependent relaxant effect of thrombocytin, a serine proteinase from Bothrops atrox snake venom, on isolated pig coronary arteries.

Since thrombin causes an endothelium-dependent relaxation of precontracted pig coronary arteries, the ability of thrombocytin, a serine proteinase from the venom of the common lancehead, Bothrops atrox, to induce endothelium-dependent changes in the vascular tone was investigated. Relaxation of pig coronary rings did not appear in vessels denuded of the endothelium. Thrombocytin (0.1-2.0 micrograms/ml) caused an endothelium-dependent, reversible, transient relaxation of PGF2 alpha-precontracted arteries which could be blocked by heparin and relatively high concentrations of alpha-NAPAP, a synthetic competitive thrombin inhibitor. Indomethacin and hirudin did not influence the relaxant effect. Both the thrombocytin- and bradykinin-induced relaxation were diminished by the guanylate cyclase inhibitor methylene blue and by NG-monomethyl-L-arginine. The thrombocytin-induced relaxation was absent in de-endothelialized vessels. Thrombocytin was able to induce aggregation of human blood platelets in Tyrode's solution at the same concentration range as used for the relaxation. Batroxobin neither relaxed precontracted arteries nor aggregated human blood platelets in vitro. The present studies show that the serine proteinase thrombocytin is not only able to aggregate platelets but may also release endothelium-derived relaxing factor from the vascular endothelium.

Animals↗
PubMed1991

Calcitonin gene-related peptide (CGRP) causes endothelium-dependent cyclic AMP, cyclic GMP and vasorelaxant responses in rat abdominal aorta.

Calcitonin gene-related peptide (CGRP), a neuropeptide found in nerves surrounding most blood vessels, is a potent hypotensive agent in both humans and rats. In isolated strips of rat thoracic aorta, CGRP has been reported to cause endothelium-dependent relaxation. To study the cellular and molecular mechanisms involved in CGRP-induced vasodilation, we investigated the roles of two second messengers, cyclic AMP and cyclic GMP, as potential mediators of the signal transduction mechanism leading to vasodilation in response to CGRP in rat aorta. In the present study, the abdominal aorta, rather than thoracic aorta, was used because of its higher content of endogenous CGRP and, therefore, the greater likelihood of regulation by CGRP in vivo. Each abdominal aortic ring was precontracted with norepinephrine (NE) at its EC50 concentration (10-20 nM). CGRP (3-300 nM) caused concentration-dependent relaxations (reducing the NE-induced contractions by 34%) that were completely dependent on endothelium. The relaxations in response to CGRP were correlated in a time- and concentration-dependent manner with increases in aortic levels of both cyclic AMP and cyclic GMP. CGRP (100 nM) caused significant elevations of cyclic AMP levels (1.4 to 3.2 pmol/mg protein, at 1 min) and cyclic GMP levels (1.6 to 3.6 pmol/mg protein, at 30 s). Like the vasorelaxant responses, both cyclic AMP and cyclic GMP responses to CGRP were totally dependent on the endothelium. Pre-incubation with indomethacin (3 microM, 15 min) did not alter cyclic AMP responses to CGRP (100 nM), suggesting that prostaglandins are not involved. Therefore, CGRP-induced vasodilations of abdominal aorta involve an endothelium-dependent mechanism associated with cyclic GMP elevations, similar to the mechanisms of vasodilation in response to acetylcholine and other endothelium-dependent vasodilators. However, CGRP-induced relaxations of aorta involve an additional mechanism (i.e., endothelium-dependent cyclic AMP elevations), which may also contribute to the intracellular mechanism of aortic vasodilation in response to CGRP.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Effects of hypoxia, mechanical and chemical endothelium denudation on guinea-pig isolated pulmonary arteries.

1. The isolated unstimulated main trunk, extralobar and intralobar branches of the pulmonary artery of the guinea-pig developed well-sustained contractions upon exposure to hypoxia (95% N2-5% CO2 gas mixture; PO2 11-15 mm Hg). The contractions were readily reversible by reoxygenation (95% O2-5% CO2). 2. Mechanical removal of the endothelium did not significantly affect the magnitude of the hypoxia-induced contractions in rings obtained from the main trunk of the pulmonary artery but reduced those of rings obtained from the proximal and distal extralobar branches. 3. Mechanical removal of the endothelium also did not affect the magnitude of contractions induced by BaCl2 in the main but significantly reduced contractions induced by the same agent in the proximal and distal extralobar branches of the pulmonary artery, suggesting that the reduction of hypoxia-induced contractions in the endothelium-denuded rings is due to impairment of vascular reactivity. 4. Pretreatment with L-N-nitro arginine, an inhibitor of the synthesis of the endothelium-derived relaxing factor, did not significantly affect the hypoxia-induced contractions but increased the magnitude of BaCl2-induced contractions in the main and the extralobar branches. 5. These observations demonstrate that isolated pulmonary artery rings of the guinea-pig develop slow contractions in response to hypoxia without prior contraction with an agonist, and that the endothelium plays little role in the hypoxia-induced contractions of guinea-pig isolated large pulmonary arteries. 6. Furthermore, these observations suggest that the effect of mechanical endothelium denudation or pharmacological manipulation, such as EDRF inhibition, on vascular reactivity should be considered when the effect of hypoxia is studied in isolated pulmonary arteries.

Animals↗
PubMed1993

Fish oil improves endothelium-dependent coronary vasodilation in heart transplant recipients.

OBJECTIVES: The purpose of this study was to determine whether dietary fish oil supplementation enhances endothelium-mediated vasodilator responses in human heart transplant recipients, a group known to have coronary artery disease and endothelial dysfunction. BACKGROUND: Omega-3 fatty acid supplementation has been shown to enhance endothelium-dependent coronary vasodilation in animal models of atherosclerosis. METHODS: Endothelium-dependent vasodilator responses to intracoronary acetylcholine infusion and endothelium-independent responses to nitroglycerin were evaluated in heart transplant recipients who received a high dose of dietary supplementation with omega-3 fatty acids for 3 weeks (5 g of eicosapentaenoic acid plus docosahexaenoic acid/day, n = 7) and compared with responses in a group of matched heart transplant recipients who did not receive fish oil (control patients, n = 7). Acetylcholine was selectively infused into the midportion of the left anterior descending or left circumflex coronary artery, with the noninfused left coronary artery serving as a control vessel. Serial coronary angiograms were performed after infusion with increasing doses of acetylcholine (infused concentrations 10(-6) to 10(-3) mol/liter) and after intracoronary nitroglycerin administration. RESULTS: The patients treated with fish oil showed a normal vasodilator response to acetylcholine with 14 +/- 2.5% and 15 +/- 7% vasodilation (vs. baseline diameter) at infused acetylcholine concentrations of 10(-5) and 10(-4) mol/liter, respectively. In contrast, the control patients demonstrated vasoconstrictor responses (-1 +/- 1% and -9 +/- 4%) to acetylcholine at these same doses (p < 0.05 and < 0.005, respectively, for treated vs. control patients). There were no differences in the response to nitroglycerin between the control and treated patients. CONCLUSIONS: Dietary supplementation with fish oil significantly alters endothelium-dependent coronary vasodilation in heart transplant recipients without alteration of the responses to endothelium-independent vasodilation. Whether this enhancement of endothelial function can beneficially alter the natural history of heart transplant atherosclerosis warrants further study.

Acetylcholine↗
PubMed1993

The dysfunctional endothelium in heart failure.

Through release of paracrine and autocrine substances, the vascular endothelium exerts a profound influence on the contractile and growth state of underlying vascular smooth muscle. In heart failure, there is now compelling evidence that endothelium-mediated relaxation is attenuated in response to muscarinic stimulation in both the coronary and peripheral circulation of humans. This impaired response is present regardless of the etiology of heart failure. The mechanisms, significance and etiologic importance of this endothelial defect are not yet understood. Possibilities include 1) alterations in endothelial cell surface receptors or abnormalities of postreceptor signal transduction; 2) abnormalities of endothelium-derived relaxing factor production or release; 3) rapid inactivation of endothelium-derived relaxing factor; and 4) an increase in endothelium-derived contracting factor production and activity in heart failure. We currently have little understanding of the mechanisms accounting for this dysfunctional state of the endothelium. Future research efforts should be directed toward an understanding of these mechanisms.

Animals↗
PubMed1994

Investigation of decreased availability of nitric oxide precursor as the mechanism responsible for impaired endothelium-dependent vasodilation in hypercholesterolemic patients.

OBJECTIVES: The purpose of this study was to determine whether the impaired endothelium-dependent vasodilation of hypercholesterolemic patients is due to decreased availability of L-arginine, the substrate for nitric oxide. BACKGROUND: Patients with hypercholesterolemia have impaired endothelium-dependent vasodilation that is related to a defect in the endothelium-derived nitric oxide system. However, the precise location of this abnormality has not been determined. METHODS: The study included 12 hypercholesterolemic patients (6 men, 6 women; 52 +/- 9 years old; serum cholesterol > 240 mg/dl) and 15 normal volunteers (8 men, 7 women; 50 +/- 6 years old; serum cholesterol < 210 mg/dl). The forearm vascular responses to intraarterial infusion of acetylcholine, an endothelium-dependent vasodilator (7.5, 15, 30 micrograms/min), and sodium nitroprusside, a direct smooth muscle dilator (0.8, 1.6, 3.2 micrograms/min) were studied before and during infusion of L- or D-arginine (a stereoisomer of arginine that is not a nitric oxide precursor). RESULTS: The response to acetylcholine was lower in hypercholesterolemic patients than in control subjects. However, no significant difference was observed with sodium nitroprusside infusion. L-Arginine augmented the response to acetylcholine in normal subjects (maximal blood flow increased from 14.4 +/- 7 to 18.9 +/- 10 ml/min per 100 ml, p < 0.002). In contrast, in the hypercholesterolemic patients, only a mild but not significant improvement in the response to acetylcholine was observed with the infusion of L-arginine (maximal blood flow increased from 6.8 +/- 4 to 8.4 +/- 5 ml/min per 100 ml; p = 0.16); however, a similar mild but not significant change was also observed with D-arginine (maximal blood flow increased from 6.8 +/- 4 to 8.3 +/- 4 ml/min per 100 ml, p = 0.07). L-Arginine did not modify the response to sodium nitroprusside in either group. CONCLUSIONS: The augmentation of endothelium-dependent vasodilation by L-arginine, the nitric oxide precursor, is defective in hypercholesterolemic patients. This supports the concept of an abnormal endothelium-derived nitric oxide system in hypercholesterolemia and indicates that decreased availability of nitric oxide substrate is not responsible for the impaired endothelial function in this condition.

Acetylcholine↗
PubMed2005

Exploring vascular benefits of endothelium-derived nitric oxide.

Although the regulation of arterial blood flow has been a subject of intensive medical research, the precise circulatory mechanisms involved are still not fully understood. It has been increasingly recognized that the endothelium plays a vital role in regulating vascular tone, structure, and function. A seminal discovery was made with the identification of endothelium-derived relaxing factor, a key mediator of vasodilation, which was later identified as nitric oxide (NO). Nitric oxide is synthesized from the amino acid L-arginine in the endothelium. Decreased bioavailability of NO is associated with arterial stiffness, hypertension, atherosclerosis, and cardiovascular disease (CVD). Nebivolol is a novel beta-blocker that is highly selective for beta1-adrenergic receptors. Nebivolol also causes vasodilation through a mechanism involving endothelium-derived NO. In clinical studies in hypertensive subjects, nebivolol significantly improves vasodilator responses to endothelium-dependent agonists such as acetylcholine. In addition, nebivolol significantly reduces pulse wave velocity (PWV), a measure of arterial stiffness, whereas the beta-blocker atenolol has no effect on PWV. Because endothelial dysfunction and arterial stiffness play an integral part in the early atherosclerotic process and are associated with poor outcomes and increased mortality, independent of blood pressure, the ability of nebivolol to enhance release of endothelium-derived NO may have significant clinical implications for the use of this agent in the treatment of hypertension and CVD.

Acetylcholine↗
PubMed2004

Plasma C-reactive protein, but not protein S, VCAM-1, von Willebrand factor or P-selectin, is associated with endothelium dysfunction in coronary artery disease.

Abnormal endothelium-dependent vasodilatation is well documented in coronary artery disease (CAD), as are significant increases of acute phase inflammatory proteins and other soluble hepatic and endothelium derived proteins. In the current study we investigated whether there is a relationship between endothelium-dependent vasodilatation and the plasma levels of such proteins. Further we examined the association between these proteins, together with age, cholesterol and endothelium function, and participant status (i.e. healthy, smoker, coronary artery disease). Three groups of participants were recruited: healthy controls (n = 20), cigarette smokers (n = 20) and patients with coronary artery disease (n = 20). Forearm vascular dilatation responses to the endothelium-dependent agonist acetylcholine were obtained using venous occlusion plethysmography. Blood was sampled at the time of study for the measurement of the serological proteins described above. Responses to acetylcholine were significantly dampened in patients with CAD when compared with control and smoker groups (forearm blood flow at acetylcholine 37 microg/min): control, smokers, CAD, 12.14 +/- 2.14, 12.35 +/- 09.4, 5.12 +/- 0.81, ANOVA, P < 0.05). Responses to acetylcholine were not different between controls and smokers. C-reactive protein (C-RP) levels (controls, smokers, CAD, 1.40 +/- 0.19, 2.27 +/- 0.71, 4.73 +/- 1.09, P < 0.05) and protein S levels were significantly higher in the CAD group compared with the other two groups. There was a significant inverse correlation between forearm blood flow responses to acetylcholine and C-reactive proteins. Both responses to acetylcholine and C-RP levels demonstrated a significant association with participant status with the r value increasing from 0.405 for responses to acetylcholine to 0.491 for the combination of responses to acetylcholine and C-RP. We conclude that there is an inverse correlation between C-reactive protein, but not protein S, VCAM-1, P-selectin nor von Willebrand factor, levels and abnormal endothelium-dependent vasodilation and further that responses to acetylcholine together with C-RP protein have a strong association with cardiovascular risk and disease.

Acetylcholine↗
PubMed2004

Endothelium-dependent hyperpolarization in small gastric arteries.

OBJECTIVE: In many blood vessels, stimulation of the endothelium with various vasoactive substances induces, besides the nitric oxide (NO) and prostacyclin pathways, a third mechanism evoking dilatation. It is based on hyperpolarization of the vascular smooth muscle cell membrane. In the present study, we investigated the existence of endothelium-dependent hyperpolarization in small gastric arteries of the rat and explored its underlying mechanism. METHODS: Membrane potentials were recorded by conventional microelectrode techniques in isolated segments of small gastric arteries, the normalized diameter of which was determined from the passive wall tension-internal circumference characteristics as measured with a myograph. RESULTS: After blocking NO and prostaglandin synthesis, application of acetylcholine (3 x 10(-7) M) resulted in a membrane hyperpolarization in endothelium intact but not in endothelium-denuded arteries. This membrane potential change was increased by pre-exposure to a low concentration (30 microM) of Ba2+, which selectively inhibits inward rectifying potassium channels. Moreover, the acetylcholine-induced hyperpolarization was unaffected by additional pre-exposure to high concentrations (0.5 mM) of the Na/K-ATPase inhibitor ouabain, which by itself caused a secondary slow endothelium-independent hyperpolarization after an initial peak depolarization. CONCLUSIONS: We conclude that acetylcholine produces endothelium-dependent hyperpolarization in gastric small arteries, which does not rely on activation of smooth muscle cell inward rectifying K+ channels or Na/K pumps, and might prove to be another important regulator of gastric mucosal blood flow.

Acetylcholine↗
PubMed2005

Enhanced external counterpulsation improves endothelium-dependent vasorelaxation in the carotid arteries of hypercholesterolemic pigs.

BACKGROUND: Enhanced external counterpulsation (EECP) has been demonstrated to be an effective method for the treatment of atherosclerotic vascular disease. However, the exact mechanism underlying the beneficial effects of EECP is not completely clear. We hypothesized that EECP leads to improvement in endothelial function, contributing to its clinical benefits. METHODS: Fifteen male domestic pigs were initially divided into 2 dietary groups: one consumed a normal feeding (NF) of pig chow (n=5), and one consumed a high-fat (HF) pig chow (n=10). After 8 weeks on the NF or HF diet, 5 HF pigs received EECP treatment (HF+EECP) 1 h daily for 6 weeks and the remaining 5 HF pigs continued to be fed by high cholesterol diet. At the end of 6-week EECP treatment, the carotid arterial rings from all of the pigs were harvested. Endothelium-dependent and -independent vasorelaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) were measured in a dose-dependent manner. RESULTS: The high fat diet resulted in increase in plasma cholesterol and triglyceride levels (p<0.05). Endothelium-dependent vasorelaxation was decreased in the HF group compared to the NF control (p<0.05). However, EECP treatment partially improved impaired endothelium-dependent vasorelaxation in the HF+EECP group compared to the HF control (p<0.05). Endothelium-independent vasorelaxation was not significantly different among the three groups. CONCLUSIONS: Endothelium-dependent vasorelaxation is impaired in the hypercholesterolemic pigs. EECP treatment significantly improves hypercholesterolemia-induced diminished endothelium-dependent vasorelaxation. It suggests that amelioration in endothelial function may at least in part contribute to the beneficial effects of EECP treatment in clinical practice.

Acetylcholine↗
PubMed2006

Modification of the Woodruff-Stamper assay demonstrates binding of Toxoplasma gondii tachyzoites to retinal vascular endothelium.

In the human host, infection with the protozoan parasite, Toxoplasma gondii, most commonly involves the eye and/or the brain. Previous work indicates a relative susceptibility of the human retinal vascular endothelium to infection with the T. gondii tachyzoite, which may contribute to this tissue localization. To facilitate the investigation of potential adhesive interactions between parasite and endothelium in the retina, we have modified the Woodruff-Stamper assay, originally described to study lymphocytic-endothelial binding. Vascular endothelium was identified in sections of human retina by Alexa Fluor 594-tagged anti-von Willebrand factor antibody. Binding of yellow fluorescent protein-expressing tachyzoites to endothelium under conditions of flow, simulated by rotation on an orbital shaker, was quantified in a masked fashion using imaging software. We observed multiple yellow spots in contact with Alexa Fluor 594-positive retina, indicating binding of T. gondii tachyzoites to retinal vascular endothelium. This modification of the Woodruff-Stamper assay provides an opportunity to evaluate potential host receptors for T. gondii on the retinal vascular endothelium. In addition, the assay suggests a methodology that could be used to examine adhesion of other microbes to microvasculature in different tissues.

Animals↗
PubMed2005

Parathyroid hormone-related protein-induced relaxation of rat uterine arteries: influence of the endothelium during gestation.

OBJECTIVE: Parathyroid hormone-related protein (PTHrP) has been reported to relax different vessels. We investigated the influence of both endothelium and gestation on the relaxation of uterine arteries (UA), which supply blood to myometrium and placenta. METHODS: Small uterine and mesenteric arteries (MA) with (E+) and without endothelium (E-) from day 20 pregnant (P) and nonpregnant (NP) rats were mounted in a myograph, precontracted with phenylephrine (PE) in a physiologic salt solution. Relaxations to PTHrP, acetylcholine, and forskolin were performed and expressed as a percentage of the PE-induced contraction. Blockade of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) was also studied with Nomega-nitro-L-arginine methyl ester (L-NAME) and with charybdotoxin + apamin, respectively. RESULTS: Gestation significantly increases maximal vasodilating effect of acetylcholine in UA (68% vs 52%, P < .05) and sensitivity to acetylcholine in small mesenteric vessels (P < .05). PTHrP relaxes uterine (maximal relaxation P: 32%, NP: 46%), as well as small MA (P: 68%, NP: 89%), but the maximal relaxation is significantly greater in NP than in P rats (P: 32%, NP: 46%, P < .01) in both vascular beds. In addition, in the UA of P rats, PTHrP only produces relaxation if functional endothelium is present; nevertheless in the absence of endothelium, forskolin still elicits relaxation (65%, P < .01). L-NAME significantly impairs relaxation of E+ UA (P < .05), and so does the association of charybdotoxin + apamin (P < .05). Thus, NO and EDHF contribute largely to this vasorelaxant effect. CONCLUSION: PTHrP induces a relaxation on UA that is strongly endothelium-dependent during gestation, in contrast to what happens simultaneously in MA.

Animals↗
PubMed1992

Endothelium-derived relaxing factor and indomethacin-sensitive contracting factor alter arterial contractile responses to thromboxane during pregnancy.

OBJECTIVES: Pregnancy reduces uterine artery contractile responses to norepinephrine and angiotensin II in many species, including the human and the guinea pig, by release of endothelium-derived relaxing substances. We hypothesized that vascular reactivity to thromboxane during pregnancy would also be reduced by a similar mechanism. STUDY DESIGN: Isolated ring segments of uterine and carotid arteries from nonpregnant and near-term pregnant guinea pigs were suspended in a myograph for the measurement of isometric tension. RESULTS: Uterine but not carotid artery sensitivity to cumulative addition of the thromboxane analog U46619 was decreased during pregnancy. The maximal contractile responses of both vessels were unaltered by pregnancy. N omega-nitro-L-arginine (10(-4) mol/L), an inhibitor of nitric oxide endothelium-derived relaxing factor synthesis, increased the sensitivity of uterine and carotid arteries to U46619 in both pregnant and nonpregnant animals. The maximal contractile response of uterine arteries from pregnant guinea pigs was also increased, but that of nonpregnant ones was not. The maximal U46619 contractile response of the carotid artery was not significantly altered by N omega-nitro-L-arginine. Indomethacin (10(-5) mol/L), a cyclooxygenase inhibitor, reduced both the sensitivity and the maximal response of U46619 in each vessel group. Removal of the endothelium from uterine artery of pregnant animals enhanced both sensitivity and maximal response to U46619. Pretreatment of the denuded segments with indomethacin reduced the sensitivity to U46619. However, indomethacin-treated denuded segments were still more sensitive to U46619 than controls. CONCLUSION: The sensitivity of guinea pig uterine artery but not carotid artery to thromboxane is reduced during pregnancy. Although the precise mechanism remains unclear, both endothelium-derived relaxing factor and an indomethacin-sensitive contracting factor are involved. If indomethacin-sensitive contracting factor is released by humans and disease alters that release, it is possible that any enhanced contractile response to thromboxane resulting from the loss of endothelium-derived relaxing agents such as prostacyclin and endothelium-derived relaxing factor would be offset by the loss of indomethacin-sensitive contracting factor.

Animals↗
PubMed1996

A comparison of endothelium-dependent relaxation in omental and myometrial resistance arteries in pregnant and nonpregnant women.

OBJECTIVES: The study aimed to compare endothelium-dependent relaxation in the resistance arteries of the uterine vascular bed by use of a systemic comparison and to investigate the role of the endothelium in adaptation to pregnancy in these vascular beds. STUDY DESIGN: Myometrial and omental resistance arteries were collected from 22 normotensive pregnant women and 27 nonpregnant women of reproductive age. On a wire myograph and preconstricted with vasopressin, the arteries were relaxed with the endothelium-dependent vasodilator bradykinin. RESULTS: The omental arteries showed a consistently greater endothelium-dependent relaxation than the myometrial arteries, both in the nonpregnant state (p < 0.0001) and in pregnancy (p = 0.008); pregnancy did not significantly alter this relaxation in arteries from either the myometrial (p = 0.2075) or omental (p = 0.372) vascular beds. CONCLUSIONS: The endothelium-dependent relaxation to bradykinin is less in myometrial resistance arteries than in omental resistance arteries. There appears to be no intrinsic difference between vessels from nonpregnant and pregnant women in endothelium-dependent response to bradykinin.

Adolescent↗
PubMed1996

Comparison of nitric oxide and prostacyclin in endothelium-dependent vasorelaxation of human umbilical artery at midgestation.

OBJECTIVE: We intended to compare the relative importance of nitric oxide and prostacyclin as endothelium-derived vasorelaxing factors released by histamine in human umbilical artery at the midstage (18 to 22 weeks) of gestation. STUDY DESIGN: By use of very thin muscle strips, which allows rapid diffusional access of applied drugs (in a few seconds), isometric tensions were recorded in response to histamine. The histamine-induced contractions and the relaxing effect of histamine on the potassium chloride (39 mmol/L) contractions were studied in relation to the existence of endothelium, L-NG-nitro arginine, and indomethacin. The relaxing effects of glyceryl trinitrate and prostacyclin on the potassium chloride contractions were also examined. RESULTS: The contractile responses to histamine were more sensitive and the relation tensions of histamine contractions, compared with the 39 mmol/L K(+)-induced contractions, were large in endothelium-denuded strips than in endothelium-intact strips. Histamine contractions were enhanced in endothelium-intact strips in the presence of 10 mumol/L L-NG-nitro arginine (competitive inhibitor of nitric oxide synthase) but not in the presence of 10 mumol/L indomethacin (cyclooxygenase inhibitor). Histamine produced a concentration-dependent relaxation during the maintained contraction induced by 39 mmol/L K+. These histamine-induced relaxations were completely blocked by L-NG-nitro arginine but not by indomethacin. Glyceryl trinitrate and prostacyclin relaxed the sustained contractions induced by 39 mmol/L K+ in a dose-dependent manner; however, the degree of relaxation by glyceryl trinitrate was more prominent than that by prostacyclin. CONCLUSION: These results suggest that nitric oxide is more potent than prostacyclin as a vasorelaxing substance released from the endothelium and that nitric oxide has an important role for controlling fetoplacental circulation at midgestation.

Endothelium, Vascular↗