The present study investigated whether or not endothelial endogenous acetylcholine contributes to relaxation. Aortic rings of spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY) were contracted with prostaglandin F_2α and exposed to progressive mild hypothermia (from 37 to 31^oC). Hypothermia-induced endothelium-dependent relaxation was reduced by atropine in SHR but not in WKY aorta. The mild hypothermia-induced relaxation in SHR aorta was inhibited by a transient receptor potential (TRP) V4 antagonist, while those in WKY aorta were reduced by a TRPA1antagonist. Thus, mild hypothermia causes nitric oxide–dependent relaxations by opening TRPA1channels in WKY aorta. By contrast, in SHR aorta, TRPV4 channels are opened, resulting in endothelial production of acetylcholine, which, in an autocrine manner, activates muscarinic receptors on neighboring cells to elicit endothelium-dependent relaxation in response to mild hypothermia.

See article at J Pharmacol Exp Ther 2015, 354:121–130.

• Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics