Endogenous acetylcholine contributes to endothelium‐dependent relaxations induced by mild hypothermia in the SHR aorta.

Abstract

The present study was designed to investigate whether or not endothelial endogenous acetylcholine contributes to endothelium‐dependent relaxations induced by mild hypothermia. Aortic rings of spontaneously hypertensive (SHR) and Wistar‐Kyoto normotensive (WKY) rats were incubated with antagonists of m‐ and n‐acetylcholine receptors (atropine and tubocurarine, respectively) or enzyme and inhibitors that can interfere with the synthesis, degradation and transport of acetylcholine (acetylcholinesterase, bromoacetylcholine, hemicholinium‐3, and vesamicol) and exposed to progressive mild hypothermia (from 37°C to 31°C) to trigger relaxations. Mild hypothermia induced endothelium‐dependent relaxations which were inhibited significantly by all the inhibitors used in SHR but not in WKY aortae. The endothelium of both SHR and WKY aortae were able to take up extracellular choline and synthesize endogenous acetylcholine. Thus, the present study demonstrates that endothelium of both normotensive and hypertensive rats can produce acetylcholine. However, mild hypothermia causes endothelium‐dependent relaxations which can be reduced by inhibiting acetylcholine receptors or interfering with the metabolism of acetylcholine only in SHR rat aortae. Thus, in the hypertensive rat, endothelial endogenous acetylcholine can in an autocrine manner activate acetylcholine receptors and elicit endothelium‐dependent relaxations.