Recovery of impaired K+ channels in mesenteric arteries from spontaneouslyhypertensive rats by prolonged treatment with cholecalciferol

1 The mechanism responsible for blood pressure reduction in spontaneously h ypertensive rats (SHR) after prolonged cholecalciferol treatment was studie d. Two-week treatment of SHR with 0.125 mg cholecalciferol kg(-1) body weig ht per day orally caused significant reductions of systolic blood pressure and of the resting perfusion pressure of the mesenteric vascular bed at con stant flow. 2 In addition, the treated animals presented a normalization of the maximum vasoconstriction response to noradrenaline and a reduction of the maximum effect of the adrenaline concentration-response curves. This latter effect probably was due to recovery of the impaired Ca2+-dependent K+ channels cou pled to alpha(2)-adrenoceptors since it was prevented by apamin. 3 The treatment with cholecalciferol also normalized the smooth muscle cell membrane potential of de-endothelialized mesenteric arteries of SHR and th eir hyperpolarizing responses to alpha(2)-adrenergic agonists, which were d epressed in untreated SHR. 4 In mesenteric rings with endothelium, alpha(2)-adrenergic agonists caused similar hyperpolarizing responses in the SHR and in normotensive Wistar (N WR) and Wistar Kyoto (WKY). In non cholecalciferol-treated SHR the hyperpol arizing mediator involved in this effect was NO, while in NWR it was the en dothelium-derived hyperpolarizing factor (EDI-IF). After cholecalciferol tr eatment, the hyperpolarization induced by alpha(2)-adrenergic agonists in S HR smooth muscle cells was mediated by EDHF, as in NWR. 5 Our results indicate that the hypotensive effect of cholecalciferol in th e SHR is probably due to the normalization of vascular reactivity, by resto ring the functioning of apamin- and ATP-sensitive K+ channels located in th e vascular smooth muscle cell membrane, which are impaired in the SHR.