Enhanced endothelium-dependent vasodilatation by dual endothelin receptor blockade in individuals with insulin resistance.

Abstract:

:Insulin resistance is associated with endothelial dysfunction and increased production of the pro-inflammatory vasoconstrictor peptide endothelin-1 (ET-1). The aim of this study was to test the hypothesis that blockade of ET receptors results in enhanced endothelium-dependent vasodilatation (EDV) in individuals with insulin resistance. Twelve individuals with insulin resistance without any history of diabetes or cardiovascular disease and 8 age-matched controls with high insulin sensitivity, as determined by hyperinsulinemic-euglycemic clamp, were investigated on 2 separate occasions using forearm venous occlusion plethysmography. Endothelium-dependent and endothelium-independent vasodilatation was determined before and after selective ET(A) and dual ET(A)/ET(B) receptor blockade. A 60 minute intraarterial infusion of the ET(A) receptor antagonist BQ123 (10 nmol/min) combined with the ET(B) receptor antagonist BQ788 (5 nmol/min) evoked a significant increase in acetylcholine-mediated EDV (P < 0.01) in individuals with insulin resistance. The endothelium-independent vasodilator response to nitroprusside was not changed by dual ET(A)/ET(B) receptor blockade. Dual ET(A)/ET(B) receptor blockade did not affect the response to acetylcholine or nitroprusside in the insulin-sensitive group. Selective ET(A) receptor blockade did not evoke any changes in endothelium-dependent or endothelium-independent vasodilatation in either group. This study demonstrates that dual ET(A)/ET(B) receptor blockade, but not selective ET(A) blockade, enhances EDV in subjects with insulin resistance, suggesting that ET-1 is involved in the regulation of endothelial function in individuals with insulin resistance.

journal_name

J Cardiovasc Pharmacol

authors

Shemyakin A,Böhm F,Wagner H,Efendic S,Båvenholm P,Pernow J

doi

10.1097/01.fjc.0000210070.47205.16

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

385-90

issue

3

eissn

0160-2446

issn

1533-4023

pii

00005344-200603000-00008

journal_volume

47

pub_type

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