Threshold concentrations of endothelin-1 potentiate contractions to norepinephrine and serotonin in human arteries. A new mechanism of vasospasm?

Yang, Zhihong; Richard, Vincent; Segesser, Ludwig von; Bauer, Erwin; Stulz, P; Turina, M; Tf, Lüscher

doi:10.1161/01.cir.82.1.188

Cited by 419 publications

(181 citation statements)

References 61 publications

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“…Moreover, there is a positive correlation between ET-1 plasma level and systolic blood pressure in humans, 9 and the vascular production of ET-1 under angiotensin II (Ang II) stimulation is higher in hypertensive than in normotensive rats. 10 The amplification is nevertheless blocked by Ca 2+ entry blocker in human arteries 4 and in the rat mesenteric bed. 6 In contrast, the direct effect of ET-1 is relatively insensitive to Ca 2+ entry blockers.…”

Section: Camentioning

confidence: 96%

“…1 Its direct contractile effect has been widely studied, although it is not yet completely understood. 2 On the other hand, subthreshold concentrations of ET-1, compatible with the plasma level, 3 potentiate the contractile effect of different agonists such as norepinephrine in human arteries 4 and rat mesenteric beds 5 - 6 and serotonin in rat aortic rings 7 and pulmonary arteries. 8 Such a phenomenon might have a pathological importance since it could be involved in hypertension and vasospastic syndrome.…”

Section: Camentioning

confidence: 97%

“…8 Such a phenomenon might have a pathological importance since it could be involved in hypertension and vasospastic syndrome. 4 Indeed, the potentiation of serotonininduced contractions by ET-1 might increase the vasospasms induced by aggregating platelets. Moreover, there is a positive correlation between ET-1 plasma level and systolic blood pressure in humans, 9 and the vascular production of ET-1 under angiotensin II (Ang II) stimulation is higher in hypertensive than in normotensive rats.…”

Section: Camentioning

confidence: 99%

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Potentiation of norepinephrine-induced contractions by endothelin-1 in the rabbit aorta.

Henrion

Laher

1993

Hypertension

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Subthreshold concentrations of endothelin-1 potentiated the norepinephrine-induced contraction in isometrically mounted rings of the rabbit aorta. Pretreatment with endothelin-1 (0.1 nM) for 10 minutes increased the sensitivity of the aortic rings to norepinephrine without affecting the maximal contraction. This amplification was unaffected by removal of the endothelium but was prevented by the protein kinase C inhibitors staurosporine (0.01 (iM) and calphostin C (0.1 fiM). Pretreatment of the aortic rings for 24 hours with phorbol 12-myristate 13-acetate (0.1 fiM) also abolished the potentiation. Norepinephrineinduced contraction was potentiated by pretreating with phorbol 12-myristate 13-acetate (10 nM) and by increasing the concentration of K + in the bath solution from 4.6 to 8.6 mM. The potentiation of the norepinephrine-induced contraction by endothelin-1 (0.1 nM) or by phorbol 12-myristate 13-acetate (10 nM) was not associated with an increase in norepinephrine-induced 45 Ca 2+ uptake or influx, whereas the potentiation due to an increase in the concentration of K + in the bath solution from 4.6 to 8.6 mM was associated with an increase in norepinephrine-induced 45 Ca 2+ uptake. We conclude that endothelin-1 potentiation of the norepinephrine-induced contraction occurs in the absence of changes in stimulated Ca 2+ entry and is endothelium independent. It is probable that endothelin-1 increases the sensitivity of the contractile apparatus to Ca 2+ by activating protein kinase C-dependent mechanisms. produced by endothelial cells. 1 Its direct contractile effect has been widely studied, although it is not yet completely understood.2 On the other hand, subthreshold concentrations of ET-1, compatible with the plasma level, 3 potentiate the contractile effect of different agonists such as norepinephrine in human arteries 4 and rat mesenteric beds 5 -6 and serotonin in rat aortic rings 7 and pulmonary arteries. 8 Such a phenomenon might have a pathological importance since it could be involved in hypertension and vasospastic syndrome.4 Indeed, the potentiation of serotonininduced contractions by ET-1 might increase the vasospasms induced by aggregating platelets. Moreover, there is a positive correlation between ET-1 plasma level and systolic blood pressure in humans, 9 and the vascular production of ET-1 under angiotensin II (Ang II) stimulation is higher in hypertensive than in normotensive rats. 10 The amplification is nevertheless blocked by Ca 2+ entry blocker in human arteries 4 and in the rat mesenteric bed. 6 In contrast, the direct effect of ET-1 is relatively insensitive to Ca 2+ entry blockers.

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Section: Camentioning

confidence: 96%

Section: Camentioning

confidence: 97%

Section: Camentioning

confidence: 99%

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Potentiation of norepinephrine-induced contractions by endothelin-1 in the rabbit aorta.

Henrion

Laher

1993

Hypertension

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“…71 In this context it is of interest that threshold and low concentrations of endothelin, which by themselves evoke no appreciable vascular effect, potentiate contractions induced by serotonin in the human coronary artery and by norepinephrine and serotonin in the human internal mammary artery. 72 Thus, OX-LDL inhibits endotheUum-dependent relaxations and promotes endotheUum-dependent as well as endothelium-independent contractions; the consequences are alterations in vascular tone leading to vasospasm and thrombus formation, both common events in patients with coronary artery disease. …”

mentioning

confidence: 99%

Endothelial Regulation of Vascular Tone and Growth

Lüscher

Tanner

1993

American Journal of Hypertension

101

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The endothelium regulates vascular tone by releasing factors involved in relaxation and contraction, in coagulation and thrombus formation, and in growth inhibition and stimulation. Endothelium-dependent relaxations are elicited by transmitters, hormones, platelet substances, and the coagulation system, and by physical stimuli such as the shear stress from circulating blood. They are mediated by the endothelium-derived relaxing factor, recently identified as nitric oxide, which causes vasodilation and platelet deactivation. Other proposed endothelium-derived relaxing factors include a hyperpolarizing factor, lipooxygenase products, and the cytochrome P450 pathway. Endothelium-derived contracting factors are produced by the cyclooxygenase pathway and by endothelial cells, which produce the peptide endothelin-1, a potent vasoconstrictor that under normal conditions circulates at low levels. The endothelium produces both growth inhibitors-normally dominant-and growth stimuli. Denuded or dysfunctional endothelium leads to a proliferative response and intimal hyperplasia in the vessel wall; moreover, platelets adhere to the site and release potent growth factors. Endothelial dysfunction has numerous causes: Aging is associated with increased formation of contracting factor and decreased relaxing factor; denudation, such as by coronary angioplasty, impairs the capacities of regenerated endothelial cells; oxidized low-density lipoproteins and hypercholesterolemia interfere with nitric oxide production; hypertension morphologically and functionally alters the endothelium; and atherosclerosis markedly attenuates some endothelium-dependent relaxations. For patients with coronary bypass grafts, differences in endotheliumderived vasoactive factors between the internal mammary artery and the saphenous vein may be important determinants of graft function, with the mammary artery having more pronounced relaxations than the saphenous vein and thus a higher patency rate. Am J Hypertens 1993;6:283S-293S KEY WORDS: Endothelial regulation, endothelial dysfunction, vascular tone, endothelium-derived relaxing factors, endothelium-derived contracting factors, nitric oxide.T he endothelium takes part in the regulation of vascular tone 1 by releasing relaxing and contracting factors both under basal conditions and when activated by neurotransmitters, hormones, autacoids, or physical stimuli. In addition, endothelial cells release factors involved in coagulation and thrombus formation and in growth inhibition and stimulation.Owing to its strategic anatomic position, the endothelium is a target organ for hypertension, diabetes, and hyperlipidemia. 1 Alterations in endothelial function may contribute to the pathogenesis as well as to the progression and complications of hypertension and its sequelae such as atherosclerotic vascular disease. ENDOTHELIUM-DEPENDENT REGULATION OF VASCULAR TONERelaxing Factors Endothelium-dependent relaxa tions occur both in vitro and in vivo 2^; transmitters, hormones, substances derived from platelets, and t...

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“…23). In addition, it potentiates the pressor effects of other vasoconstrictive substances, such as ANG II (47), norepinephrine, and serotonin (45), and promotes the proliferation of vascular smooth muscle cells (12) and cardiac fibroblasts (31), which may thicken the vascular wall. Central administration of ET-1 also increases sympathetic nerve activity and blood pressure via ET A R (30).…”

mentioning

confidence: 99%

Insulin infusion induces endothelin-1-dependent hypertension in rats

Juan¹,

Shen²,

Chien³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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. Metabolism 48: [465][466][467][468][469][470][471] 1999). Endothelin-1 (ET-1), a potent vasoconstrictor, is suggested to play an important role in maintaining vascular tone and regulating blood pressure, and insulin increases ET-1 production in vivo and in vitro. In the present study, BQ-610, a selective endothelin A receptor antagonist, was used to examine the role of ET-1 in insulin-induced hypertension in rats. BQ-610 (0.7 mg/ml; 0.5 ml/kg body wt) or normal saline was given intraperitoneally two times daily for 25 days to groups of rats infused with either saline or insulin (2 U/day via sc-implanted osmotic pumps), and changes in plasma levels of insulin, glucose, and ET-1 and the systolic blood pressure were measured over the experimental period, whereas changes in insulin sensitivity were examined at the end of the experimental period. Plasma insulin and ET-1 levels were measured by RIA, plasma glucose levels using a glucose analyzer, systolic blood pressure by the tail-cuff method, and insulin sensitivity by an oral glucose tolerance test. Our studies showed that insulin infusion caused sustained hyperinsulinemia in both saline-and BQ-610-injected rats over the infusion period. After pump implantation (2 wk), the systolic blood pressure was significantly higher in insulin-infused rats than in saline-infused rats in the saline-injected group (133 Ϯ 3.1 vs. 113 Ϯ 1.1 mmHg, P Ͻ 0.05) but not in the BQ-610-injected group (117 Ϯ 1.2 vs. 117 Ϯ 1.8 mmHg). Plasma ET-1 levels in both sets of insulin-infused rats were higher than in saline-infused controls (2.5 Ϯ 0.6 and 2.5 Ϯ 0.8 vs. 1.8 Ϯ 0.4 and 1.7 Ϯ 0.3 pmol/l, P Ͻ 0.05). Oral glucose tolerance tests showed that BQ-610 treatment did not prevent the insulin resistance caused by chronic insulin infusion. No significant changes were found in insulin sensitivity and blood pressure in saline-infused rats treated with BQ-610. In a separate experiment, insulin infusion induced the increase in arterial ET-1 content, hypertension, and subsequent plasma ET-1 elevation in rats. These results suggest that, in the insulin infusion rat model, ET-1 plays a mediating role in the development of hypertension, but not of insulin resistance. hyperinsulinemia; insulin resistance; endothelin A receptor EPIDEMIOLOGICAL STUDIES HAVE revealed an association between hyperinsulinemia and a number of metabolic disorders, including glucose intolerance, dyslipidemia, and hypertension (25). This association is often seen in patients with type 2 diabetes, obesity, atherosclerotic cardiovascular diseases, and hypertension and is therefore referred to as syndrome X (33), or insulin resistance syndrome (4). However, no pathological relationship between hyperinsulinemia and hypertension has been established in this syndrome (11). When rats are fed a diet in which the entire carbohydrate intake is pure fructose, glucose, or sucrose, they develop insulin resistance with hyperinsulinemia and hypertension, thus mimicking the human syndrome (29). These associated abnormalities are also seen in rats...

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Threshold concentrations of endothelin-1 potentiate contractions to norepinephrine and serotonin in human arteries. A new mechanism of vasospasm?

Cited by 419 publications

References 61 publications

Potentiation of norepinephrine-induced contractions by endothelin-1 in the rabbit aorta.

Potentiation of norepinephrine-induced contractions by endothelin-1 in the rabbit aorta.

Endothelial Regulation of Vascular Tone and Growth

Insulin infusion induces endothelin-1-dependent hypertension in rats

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