IMPAIRED FUNCTION OF ALPHA-2-ADRENOCEPTORS IN SMOOTH-MUSCLE OF MESENTERIC-ARTERIES FROM SPONTANEOUSLY HYPERTENSIVE RATS

1 The alpha(2)-adrenoceptor function in mesenteric arteries of spontan eously hypertensive rats (SHR) was investigated by comparing membrane potential changes in response to adrenergic agonists in preparations f rom female SHR, Wistar-Kyoto (WKY) and normotensive Wistar rats (NWR). 2 Resting membrane potential was found to be less negative in mesente ric arteries from SHR than in those from NWR and WKY. Apamin induced a decrease in the membrane potential of mesenteric artery rings without endothelium from NWR and WKY, but had no effects in those from SHR. B oth UK 14,304 and adrenaline, in the presence of prazosin, induced a h yperpolarization that was significantly lower in de-endothelialized me senteric rings from SHR than in those from NWR and WKY. In mesenteric rings with endothelium, however, similar hyperpolarization was observe d in the three strains. 3 In NWR mesenteric rings with endothelium the hyperpolarization induced by activation of alpha(2)-adrenoceptors was abolished by apamin, whereas in intact SHR mesenteric rings this hype rpolarization was slightly reduced by apamin and more efficiently redu ced by N-omega-nitro-L-arginine. 4 It is concluded that the activity o f potassium channels coupled to alpha(2)-adrenoceptors is altered in t he smooth muscle cells of SHR mesenteric arteries, contributing to the ir less negative membrane potential. On the other hand, the endothelia l alpha(2)-receptors are functioning in mesenteric vessels from SHR an d their stimulation induces a hyperpolarization mainly through the rel ease of nitric oxide.