Endothelin is a positive inotropic agent in human and rat heart in, vitro

Moravec, Christine S.; Reynolds, Elwood E.; Stewart, Robert W.; Bond, Meredith

doi:10.1016/0006-291x(89)92397-8

Cited by 214 publications

(72 citation statements)

References 9 publications

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“…It is possible that ET contributes to or regulates vascular compliance of larger conduit arteries and, in turn, affects systolic blood pressure in particular. ET also has positive inotropic properties 26 ; hence, an ET antagonist might reduce stroke volume. The small increase in heart rate must be due to unloading baroreceptors, with activation of the sympathetic nervous system.…”

Section: Discussionmentioning

confidence: 99%

Hemodynamic and Coronary Effects of the Endothelin Antagonist Bosentan in Patients With Coronary Artery Disease

et al. 1998

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Background-Endothelin is a potent endothelium-derived vasoconstrictor peptide with proliferative properties. Elevated levels of the peptide occur in coronary artery disease; however, its pathophysiological role as a regulator of coronary tone and structure is uncertain. Endothelin-receptor antagonists are specific tools to clarify this issue and might be useful in the treatment of coronary artery disease. Methods and Results-In a double-blind, placebo-controlled randomized study, we investigated the effects of the ET A /ET B endothelin-receptor antagonist bosentan or placebo on systemic and coronary hemodynamics in 28 patients with angiographically documented stable coronary artery disease by quantitative coronary angiography and an intracoronary Doppler guidewire. Bosentan 200 mg IV decreased systolic blood pressure (PϽ0.05), whereas heart rate increased slightly (PϽ0.05). Coronary diameter increased, particularly in vessels with no or mild angiographic changes (PϽ0.01). Glycerol trinitrate did not further dilate these segments, whereas coronary diameter increased significantly after nitrate in the placebo group. The increase in coronary diameter after bosentan correlated inversely with plasma LDL-cholesterol levels (PϽ0.01) in both stenotic and angiographically normal coronary segments. Coronary flow velocity did not change. Bosentan was well tolerated. Conclusions-Endogenous endothelin exerts a vasoconstrictor tone in epicardial coronary arteries of patients with coronary artery disease, as evidenced by the vasodilation exerted by the combined ET A /ET B endothelin-receptor antagonist bosentan under acute conditions. Bosentan can safely be given to these patients. Hence, further long-term studies are necessary to determine the therapeutic potential of endothelin-receptor antagonists in patients with coronary artery disease. (Circulation. 1998;98:2235-2240.)

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Section: Discussionmentioning

confidence: 99%

Hemodynamic and Coronary Effects of the Endothelin Antagonist Bosentan in Patients With Coronary Artery Disease

et al. 1998

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“…Endothelin has previously been shown to elicit positive inotropic responses in the human isolated atrium (Davenport et al 1989;Brodde et al 1992). However, ET-1 did not cause positive inotropic affects in six strips obtained from the human ventricle strip that responded normally to (-)-isoprenaline (Davenport et al 1989) and caused only very small inotropic effects in another study (Moravec et al 1989). In this respect, it is of interest that the receptor density in the ventricle of several animal species has previously been found to correspond to the effectiveness of ET-1 in producing a positive inotropic effect (Takanashi and Endoh 1991).…”

Section: Endothelin Receptors In the Ventricle And The Atriummentioning

confidence: 93%

“…Endothelin has been shown to cause positive inotropic and/or chronotropic effects in the ventricle and atrium of several animal species (Kitayoshi et al 1989;Ishikawa et al 1988a, b) and man (Moravec et al 1989;Davenport et al 1989;Brodde et al 1992). In the rabbit isolated papillary muscle, the positive inotropic response appeared to be mediated by the ET B receptor (Takanashi and Endoh 1991), but the nature of the receptor involved in endothelin-induced rat myocyte hypertrophy and secretion of natriuretic peptide from rat myocytes (Shubeita et al 1990) thus far remains unknown.…”

Section: Endothelin Receptors In the Ventricle And The Atriummentioning

confidence: 99%

“…In addition, Fozard and Wright (1988) described a vasodilatory effect, later found to be mediated, at least partially, by an endothelium-dependent mechanism involving the release of nitric oxide (NO; Fukuda et al 1990) and/or prostacyclin (PGI2; De Nucci et al 1990). In the heart, endothelin has been reported to elicit both positive inotropic (Moravec et al 1989;Kitayoshi et al 1989;Takanashi and Endoh 1991) and chronotropic (Ishikawa et al 1989) effects. Furthermore, endothelin induced mitogenesis of vascular smooth muscle cells (Komuro et al 1988;Ohlstein et al 1992) and hypertrophy of myocardial cells (Shubeita et al 1990) indicating that endothelin may play a role in the development of atherosclerosis and cardiac hypertrophy.…”

Section: Introductionmentioning

confidence: 99%

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Endothelin receptors in the human coronary artery, ventricle and atrium

Bax

Bruinvels

Suylen

et al. 1993

Naunyn-Schmiedeberg's Arch Pharmacol

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Summary.In the present experiments we investigated endothelin (ET) receptors in the human coronary artery, and in ventricular and atrial muscle using quantitative receptor autoradiography. These data indicate that both [125I]ET-1 and [125I] Sf6b-labeled ETA and ETB binding sites in human ventricular and atrial muscle. In the human coronary artery, both radioligands labeled ETA binding sites, but [125I] Sf6b also labeled a non-ET A, non-ETB binding site with relatively high affinity for both ET-1.

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“…ET exerts a strong, dose-dependent positive inotropic effect on the myocardium. 22 - 23 Blockers of /3-adrenergic, a-adrenergic, serotonergic, and histaminergic receptors and pretreatment with indomethacin failed to inhibit the inotropic action of ET, suggesting a direct effect on the myocardium. ET appears to augment inotropic activity by elevating cytosolic free [Ca 2+ ], either by increasing the opening probability of L-type, voltage-activated Ca 2+ channels or by increasing activity of the phosphoinositide cascade with subsequent release of intracellular Ca 2+ from the inositol 1,4,5-trisphosphate (Ins[l,4,5]P 3 )-sensitive intracellular stores.…”

Section: Hjq]d[v]i Wmentioning

confidence: 97%