Diminished beta-adrenoceptor-mediated relaxation of femoral arteries from young spontaneously hypertensive rats

A beta -adrenoceptor agonist, norepinephrine (NE)-induced relaxation in the presence of an alpha -adrenoceptor antagonist and indomethacin was investi gated in isolated femoral arteries from 5-week-oId Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). NE elicited endothelium-dependen t and -independent relaxation in WKY. In endothelium-intact WKY artery, the NE-induced relaxation was reduced by nitro L-arginine (L-NA) and methylene blue. The residual response to NE in the presence of L-NA was further redu ced by tetraethylammonium (TEA). Glibenclamide attenuated the NE-induced, e ndothelium-independent relaxation in WKY. In SHR, on the other hand, the re laxation to NE was solely endothelium-independent, unaffected by a combinat ion of L-NA and TEA and inhibited by glibenclamide. The relaxation in respo nse to NE in SHR was less than that in WKY, regardless of the presence and absence of endothelial cells. When WKY and SHR were treated for 10 days wit h captopril, the response to NE was increased not only in WKY but also in S HR. The relaxation in captopril-treated SI-IR consisted of endothelium-depe ndent and -independent components. The former was attenuated by L-NA and to a greater extent by TEA with L-NA. Sodium nitroprusside- and forskolin-ind uced, endothelium-independent relaxations in SHR were not significantly dif ferent from those in WKY. Captopril did not affect the response to these dr ugs. The present results indicate that the relaxation to NE is in part medi ated by NO and a vasorelaxing factor distinct from NO in WKY but not in SHR . It is suggested that NE-induced, endothelium-independent relaxation in bo th groups is in part mediated by ATP-sensitive K+ channels. It is also sugg ested that in SHR, captopril increases the response to NE through increases in endothelial production of NO and the non-NO vasorelaxing factor. (C) 20 01 Elsevier Science B.V. All rights reserved.