Estrogen receptor-mediated vascular responsiveness to nebivolol: a novel endothelium-related mechanism of therapeutic vasorelaxation.

Abstract:

:Nebivolol is a highly selective and lipophilic beta1-adrenergic receptor antagonist with vasodilating characteristics attributed mainly to endothelial generation of nitric oxide (NO). Coincidently, rapid vascular vasodilating effects of estradiol are also widely reported and membrane-initiated signaling by estrogen receptor (ER), leading to generation of NO, parallels the vasodilating effects observed for nebivolol. Thus, we hypothesized that the NO-dependent vasodilating effect attributed to nebivolol may be partially mediated through its interaction with the membrane-associated form of ER. The objective of this study was to examine the ER-mediated/endothelium-dependent vascular responses to nebivolol and the specific binding properties of nebivolol to ER. In isolated rat aortic rings, the endothelium-dependent vasodilating effect of nebivolol was significantly blocked by the use of the potent ER antagonist, ICI 182,780. In contrast, in the absence of intact endothelium, nebivolol-induced vasorelaxation was not blocked by ICI 182,780, strongly suggesting that nebivolol-elicited vasorelaxation is partially dependent on ER-mediated pathways. Further, we examined the binding of nebivolol to ER (MCF-7 cells) by radioligand binding assay and revealed specific binding kinetics with an estimated DC50 of 5 x 10 M, coinciding with the approximate EC50 of nebivolol as a vasorelaxant. In conclusion, the endothelium-dependent vascular response to nebivolol is attributed partially to its interaction with ER.

journal_name

J Cardiovasc Pharmacol

authors

Garbán HJ,Buga GM,Ignarro LJ

doi

10.1097/00005344-200405000-00005

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

638-44

issue

5

eissn

0160-2446

issn

1533-4023

pii

00005344-200405000-00005

journal_volume

43

pub_type

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