Endothelium-dependent relaxation counteracting the contractile action of endothelin-1 is partly due to ETB receptor activation

Feger, G. I.; Schilling, Lothar; Ehrenreich, Hannelore; Wahl, Michael

doi:10.1007/bf02576857

Cited by 16 publications

(10 citation statements)

References 40 publications

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“…The effects of low endothelin-1 concentrations on endothelin ETB receptors localized on the endothelium dominate the action of the peptide on contractions induced by 5-HT, though the contractile endothelin ETA receptors were not blocked in our experiments. In contrast to these findings, Feger et al (1997) reported that a relaxant action of endothelin-1 (when administered to a precontracted segment of the rat basilar artery) can only be detected in the presence of BQ-123 to block the contractile endothelin ETA receptors. Thus, though threshold concentrations of endothelin-1 elicit small contractions, the relaxant effect of endothelin-1 is substantially unmasked in our experiments when the peptide is given before other vasoactive substances are administered.…”

Section: Inhibitory Eflects Of Endothelin-1 In the Basilar Arterymentioning

confidence: 54%

Threshold Concentrations of Endothelin‐1: The Effects on Contractions Induced by 5‐Hydroxytryptamine in Isolated Rat Cerebral and Mesenteric Arteries *

Hempelmann¹,

Pradel²,

Mehdorn³

et al. 1999

Pharmacology & Toxicology

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Ahsrruct; This study compares the effects of threshold concentrations of endothelin-1 in isolated rat basilar arteries with those in mesenteric arterial branches and investigates the mechanisms of inhibitory and potentiating endothelin-I-effects. In basilar arteries, endothelin-1 reduces the contractions induced by 5-hydroxytryptamine (5-HT), by the thromboxane A2 agonist U46619, and by vasopressin. The inhibitory effect of endothelin-1 on the contraction induced by 5-HT is abolished by deendothelialization, by the endothelin ETB receptor antagonist RES 701-1, by indomethacin, or by glibenclamide. In mesenteric arteries, endothelin-1 potentiates the contractile effects of 5-HT, U46619, and vasopressin. The potentiation of the contractile effect induced by 5-HT is only somewhat modified by deendothelialization, but abolished by the thromboxane A2 receptor antagonists GR32191 and ridogrel. U46619 potentiates the 5-HT-effect in mesenteric arteries. Thus, though the contractile endothelin ETA receptors were not blocked, threshold concentrations of endothelin-I inhibited contractile effects in the rat basilar artery via activation of endothelial ETB receptors. Prostaglandins and ATP-sensitive K+ channels are involved in this inhibitory action. In contrast, endothelin-1 potentiates contractile actions in mesenteric arteries via the release of endogeneous thromboxane A2 from non-endothelial cells. The study points out the completely different role of the endothelium in combined effects of endothelin-1 between cerebral and mesenteric arteries.

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Section: Inhibitory Eflects Of Endothelin-1 In the Basilar Arterymentioning

confidence: 54%

Threshold Concentrations of Endothelin‐1: The Effects on Contractions Induced by 5‐Hydroxytryptamine in Isolated Rat Cerebral and Mesenteric Arteries *

Hempelmann¹,

Pradel²,

Mehdorn³

et al. 1999

Pharmacology & Toxicology

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“…1,2 This mechanism is essentially supported by demonstrations that NOS inhibitor enhanced the constrictor effects of exogenous ET-1 in several in vivo and ex vivo preparations. [3][4][5][6][7][8][9][10][11][12][13][14] Thus, an assumption underlying these observations is that the constrictor actions of exogenous and endogenous ET-1 are similarly affected by NO; (2) NO inhibition of ET-1 release. 1,2 Although the detailed mechanism underlying the NO inhibition of acute ET-1 release has not been clearly established, possibilities include decreased conversion of the immediate precursor to ET-1, big ET-1, to ET-1 15 and inhibition of pathways involved in the exocytosis of Weibel-Palade bodies, 16 endothelial granules that store ET-1.…”

Section: • Online Data Supplementmentioning

confidence: 99%

Nitric Oxide Inhibition of Endothelin-1 Release in the Vasculature

Rapoport

2014

Hypertension

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A key function of endothelial derived nitric oxide (NO) is to limit the constrictor capacity of endothelin (ET)-1.1,2 Thus, an imbalance between NO and ET-1 can result in ET-1-dependent increased vascular tone.1 Indeed, the importance of sustained, NO inhibition of the ET-1 drive to increase tone is exemplified in vivo by the rapid, ET-1-mediated arterial pressure elevation after acute NO synthase (NOS) inhibition. Moreover, the ET-1 pressor effect after NOS inhibition is independent of other pressor systems and, thus, reflects the relative importance of NO suppression of this ET-1 drive.2 Two, nonmutually exclusive mechanisms thought to underlie the ET-1 dependency of the increased vascular tone responsible for the NOS inhibitor-induced pressure elevation are (1) NO inhibition of constriction to endogenously released ET-1.1,2 This mechanism is essentially supported by demonstrations that NOS inhibitor enhanced the constrictor effects of exogenous ET-1 in several in vivo and ex vivo preparations. 3-14Thus, an assumption underlying these observations is that the constrictor actions of exogenous and endogenous ET-1 are similarly affected by NO; (2) NO inhibition of ET-1 release. 1,2Although the detailed mechanism underlying the NO inhibition of acute ET-1 release has not been clearly established, possibilities include decreased conversion of the immediate precursor to ET-1, big ET-1, to ET-1 15 and inhibition of pathways involved in the exocytosis of Weibel-Palade bodies, 16 endothelial granules that store ET-1. 17 However, it should be noted that in vivo findings that actually demonstrate the fundamental phenomenon of NO inhibition of ET-1 release are generally lacking.2 Thus, studies purported to demonstrate NO inhibition of ET-1 release have relied largely on isolated vessels and cultured endothelium, as described herein.This review assessed these in vitro findings, with a specific focus toward elucidating the mechanism underlying the NO-mediated negative regulation of ET-1-dependent increased arterial pressure, as demonstrated after acute NOS inhibitor in vivo.2 Findings referred to are mainly those of ET-1 release rather than contractility (eg, those in which ET receptor antagonist prevented the NOS inhibitor-induced decreased flow/increased pressure/tension). 12,18-25 The rationale for this emphasis is that findings based on contractility could reflect NOS inhibitor enhancement of ET-1 constriction rather than increased ET-1 release. Furthermore, we also focus on whether laminar shear stress influences the manifestation of NO inhibition of ET-1 release. That is, the endothelium of arteries that are anatomically linear is subjected to high levels of shear stress while, for example, at bifurcated arterial locations is subjected to low levels of shear stress, regions associated with atherosclerosis. 26 Acute NOS Inhibition/No Donors and ET-1 Release ArteriesIn rat heart perfused at constant flow, increased amounts of ET-1 were detected in the coronary effluent of samples collected for the final 5 to 15 minutes ...

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“…The Prostate DOI 10.1002/pros [67]. Rapid blood flow reduction observed with IRL-1620 in the P22 tumor and the HSN sarcoma [64] might be due to the existence of larger population of VSMCs in the sarcoma (muscle) tumor model employed for the study and/or may be attributed to doses of ET B receptor agonists used.…”

Section: Discussionmentioning

confidence: 99%

IRL‐1620, a tumor selective vasodilator, augments the uptake and efficacy of chemotherapeutic agents in prostate tumor rats

2007

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Endothelium-dependent relaxation counteracting the contractile action of endothelin-1 is partly due to ETB receptor activation

Cited by 16 publications

References 40 publications

Threshold Concentrations of Endothelin‐1: The Effects on Contractions Induced by 5‐Hydroxytryptamine in Isolated Rat Cerebral and Mesenteric Arteries *

Threshold Concentrations of Endothelin‐1: The Effects on Contractions Induced by 5‐Hydroxytryptamine in Isolated Rat Cerebral and Mesenteric Arteries *

Nitric Oxide Inhibition of Endothelin-1 Release in the Vasculature

IRL‐1620, a tumor selective vasodilator, augments the uptake and efficacy of chemotherapeutic agents in prostate tumor rats

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