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

Journal of Cardiovascular Pharmacology
Alexey ShemyakinJ Pernow

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 acetyl...Continue Reading

Citations

Apr 19, 2011·Journal of Medical Case Reports·Fátima Alvarez ReyesManuel Brito Suárez
Jan 12, 2013·Reviews in Endocrine & Metabolic Disorders·Ranganath Muniyappa, James R Sowers
Feb 12, 2013·Reviews in Endocrine & Metabolic Disorders·Kieren J Mather
Dec 5, 2019·Frontiers in Physiology·Xinguo JiangStanley G Rockson

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