Effect of cholecalciferol treatment on the relaxant responses of spontaneously hypertensive rat arteries to acetylcholine

We studied the effect of oral cholecalciferol treatment on the endothelium- dependent vascular relaxation and hyperpolarization induced by acetylcholin e (ACh), which is impaired in spontaneously hypertensive rats (SHR). Adult female SHR and normotensive Wistar-Kyoto rat (WKY) controls received 125 mu g of cholecalciferol per kilogram body weight per day for 6 weeks. The res ponses to ACh of the isolated mesenteric vascular bed and mesenteric artery rings were measured, as well as the smooth muscle cell membrane potential. After cholecalciferol treatment, the systolic blood pressure and basal per fusion pressure of the mesenteric vascular bed of the SHR fell to control l evels. The relaxant and hyperpolarizing effects of ACh, which are reduced i n SHR, were also brought to control levels after cholecalciferol treatment. These effects of ACh were inhibited by N-omega-nitro-L-arginine in SHR and by apamin in WKY. After cholecalciferol treatment, SHR hyperpolarizing res ponses showed the same inhibition pattern as those of WKY. This indicates t hat, after cholecalciferol treatment, SHR vascular mesenteric preparation r esponses to ACh are mediated by endothelium-derived hyperpolarizing factor, which induces activation of Ca2+-dependent K+ channels, as in WKY. In untr eated SHR, the ACh-mediated response is entirely due to ACh acting via the release of nitric oxide.