Mechanisms underlying diabetes enhancement of endothelin-1-induced contraction in rabbit basilar artery

6533b822fe1ef96bd127ce4a

RESEARCH PRODUCT

Mechanisms underlying diabetes enhancement of endothelin-1-induced contraction in rabbit basilar artery

José M. Centeno Vannina G. Marrachelli José A. Alabadí Silvia Llorens Enrique Alborch Francisco J. Miranda

subject

Endothelin Receptor Antagonists Male Nitroprusside medicine.medical_specialty Contraction (grammar)Vascular smooth muscle Endothelium Endothelin A Receptor Antagonists Vasodilator Agents Endothelin B Receptor Antagonists Nitroarginine Peptides Cyclic Muscle Smooth Vascular Diabetes Mellitus Experimental Piperidines Isometric Contraction medicine.artery Internal medicine medicine Basilar artery Animals Enzyme Inhibitors Antihypertensive Agents Pharmacology Diabetis Endothelin-1 Artèries business.industry Endoteli vascular Receptor Endothelin A Receptor Endothelin B Endothelin 1 Òxid nítric Endothelin A Receptor Antagonists Endothelin B Receptor Antagonists Endocrinology medicine.anatomical_structure Basilar Artery cardiovascular system Rabbits business Endothelin receptor Oligopeptides

description

The influence of alloxan-induced diabetes on the reactivity of rabbit basilar artery to endothelin-1 was examined. Endothelin-1 induced concentration-dependent contraction of basilar arteries that was higher in diabetic than in control rabbits. Endothelium removal produced a higher enhancement of the endothelin-1-induced contraction in control than in diabetic rabbits. N(G)-nitro-L-arginine (L-NOArg) enhanced the maximal contraction induced by endothelin-1 in control rabbits and potentiated this response in diabetic rabbits. Endothelin ETA receptor antagonist, cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123), inhibited endothelin-1-induced contraction in both rabbit groups. Endothelin ETB receptor antagonist, 2,6-Dimethylpiperidinecarbonyl-gamma-Methyl-Leu-Nin-(Methoxycarbonyl)-D-Trp-D-Nle (BQ-788), enhanced endothelin-1-induced contraction in control rabbits and decreased the potency of endothelin-1 in diabetic rabbits. Sodium nitroprusside-induced relaxation of basilar arteries was lower in diabetic than in control rabbits. These results suggest that mechanisms underlying rabbit basilar artery hyperreactivity to endothelin-1 include decreased endothelial modulation of endothelin-1-induced contraction, with impaired endothelial endothelin ETB receptor activity; decreased sensitivity to nitric oxide (NO) in vascular smooth muscle; and enhanced participation of muscular endothelin ETA and ETB receptors.

year	journal	country	edition	language
2004-01-01	European Journal of Pharmacology

https://doi.org/10.1016/j.ejphar.2004.01.005