Effect of chronic and selective endothelin receptor antagonism on microvascular function in type 2 diabetes.

American Journal of Physiology. Heart and Circulatory Physiology
Kamakshi SachidanandamA Ergul

Abstract

Vascular dysfunction, which presents either as an increased response to vasoconstrictors or an impaired relaxation to dilator agents, results in worsened cardiovascular outcomes in diabetes. We have established that the mesenteric circulation in Type 2 diabetes is hyperreactive to the potent vasoconstrictor endothelin-1 (ET-1) and displays increased nitric oxide-dependent vasodilation. The current study examined the individual and/or the relative roles of the ET receptors governing vascular function in the Goto-Kakizaki rat, a mildly hyperglycemic, normotensive, and nonobese model of Type 2 diabetes. Diabetic and control rats received an antagonist to either the ET type A (ETA; atrasentan; 5 mg x kg(-1) x day(-1)) or type B (ET(B); A-192621; 15 or 30 mg x kg(-1) x day(-1)) receptors for 4 wk. Third-order mesenteric arteries were isolated, and vascular function was assessed with a wire myograph. Maximum response to ET-1 was increased in diabetes and attenuated by ETA antagonism. ETB blockade with 15 mg/kg A-192621 augmented vasoconstriction in controls, whereas it had no further effect on ET-1 hyperreactivity in diabetes. The higher dose of A-192621 showed an ETA-like effect and decreased vasoconstriction in diabetes. Maximum re...Continue Reading

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Citations

Jul 8, 2011·The British Journal of Nutrition·Moonyeon YounDaniel D Gallaher
Oct 23, 2008·The Journal of Pharmacology and Experimental Therapeutics·Kamakshi SachidanandamAdviye Ergul
Jan 30, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Kamakshi SachidanandamAdviye Ergul
Jul 16, 2010·Canadian Journal of Physiology and Pharmacology·Kamakshi SachidanandamAdviye Ergul
Aug 21, 2010·Canadian Journal of Physiology and Pharmacology·Weiguo LiAdviye Ergul
Feb 5, 2011·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Adviye Ergul
Nov 19, 2015·Pflügers Archiv : European journal of physiology·Shun WatanabeTsuneo Kobayashi
Dec 16, 2016·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Joy S ShomeAmedeo Chiribiri
Jun 3, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Kyan J AllahdadiNancy L Kanagy
Mar 17, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Takayuki MatsumotoKatsuo Kamata
Sep 16, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·ChengCheng LinYuanShao Lin
Oct 11, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Mieke van den HeuvelWillem J van der Giessen

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