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

Abstract

A β-adrenoceptor agonist, norepinephrine (NE)-induced relaxation in the presence of an α-adrenoceptor antagonist and indomethacin was investigated in isolated femoral arteries from 5-week-old Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). NE elicited endothelium-dependent 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 reduced by tetraethylammonium (TEA). Glibenclamide attenuated the NE-induced, endothelium-independent relaxation in WKY. In SHR, on the other hand, the relaxation to NE was solely endothelium-independent, unaffected by a combination of l-NA and TEA and inhibited by glibenclamide. The relaxation in response 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 with captopril, the response to NE was increased not only in WKY but also in SHR. The relaxation in captopril-treated SHR consisted of endothelium-dependent and -independent components. The former was attenuated by l-NA and to a greater extent by TEA with l-NA. Sodium nitroprusside- and forskolin-induced, endothelium-independent relaxations in SHR were not significantly different from those in WKY. Captopril did not affect the response to these drugs. The present results indicate that the relaxation to NE is in part mediated 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 both groups is in part mediated by ATP-sensitive K + channels. It is also suggested that in SHR, captopril increases the response to NE through increases in endothelial production of NO and the non-NO vasorelaxing factor.