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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2359.)
© 2000 American Heart Association, Inc.

Vascular Biology

Thiol Oxidation Activates a Novel Redox-Regulated Coronary Vasodilator Mechanism Involving Inhibition of Ca²⁺ Influx

Presented in part at the Experimental Biology ’99 Meeting, Washington, DC, April 17–21, 1999, and published in abstract form (FASEB J. 1999;13:A198) and at the 72nd Scientific Sessions of the American Heart Association, Atlanta, Ga, November 7–10, 1999, and published in abstract form (Circulation. 1999;100[suppl I]:I-418).

Takafumi Iesaki; Michael S. Wolin

From the Department of Physiology, New York Medical College, Valhalla, NY.

Correspondence to Michael S. Wolin, PhD, Department of Physiology, New York Medical College, Valhalla, NY 10595. E-mail mike_wolin{at}nymc.edu

Abstract—This study examines the mechanism of relaxation of isolated endothelium-removed bovine coronary arteries (BCAs) to the thiol oxidant diamide. BCAs precontracted with KCl or the thromboxane A₂ receptor agonist U46619 showed a concentration-dependent reversible relaxation on exposure to 10 µmol/L to 1 mmol/L diamide. This relaxation was enhanced by an inhibitor of glutathione reductase, and it was not altered by severe hypoxia, the presence of inhibitors of soluble guanylate cyclase, K⁺ channels, tyrosine kinases, or probes that modulate levels of superoxide. The relaxation was almost eliminated when BCAs were precontracted with a phorbol ester that causes a contraction that is largely independent of extracellular Ca²⁺. The initial transient contraction elicited by 5-hydroxytryptamine in Ca²⁺-free solution was not altered by the presence of 1 mmol/L diamide; however, a subsequent tonic contraction on addition of CaCl₂ was inhibited by diamide. Diamide also inhibited contractions caused by the addition of CaCl₂ to Ca²⁺-free Krebs’ buffer containing Bay K8644 (an L-type Ca²⁺ channel opener) or KCl. Relaxation to diamide was attenuated by L-type Ca²⁺ channel blockers (nifedipine and diltiazem). Thus, thiol oxidation elicited by diamide appears to activate a novel redox-regulated vasodilator mechanism that seems to inhibit extracellular Ca²⁺ influx.

Key Words: calcium • diamide • redox signaling • thiol redox • vasodilation

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