ALPHA(1)-ADRENOCEPTOR SUBTYPES MEDIATING CONTRACTION OF THE FEMORAL-ARTERY IN SPONTANEOUSLY HYPERTENSIVE RATS

alpha(1)-Adrenoceptors (ARs) were divided into alpha(1H) and alpha(1L) subtypes by their different affinities for bunazosin or prazosin. alpha(1H)-ARs were further subdivided into alpha(1A), alpha(1B), and alpha(1C) subtypes. Therefore, this study was undertaken to determine which alpha(1)-AR subtypes were involved in the activation of femoral artery preparations by alpha(1)-AR agonists in spontaneously hypertensive rats (SHR). For comparison, aortic strips were also incorporated in the present study. In the presence of propranolol, deoxycorticosterone, and desipramine, norepinephrine (NE) contracted the vascular strips in a dose-dependent manner. Negative log EC(50) values and maximum responses of NE-induced contraction of the SHR femoral artery were unchanged and increased, respectively, compared with those of Sprague-Dawley and Wistar-Kyoto rats (WKY). Contractile responses of the SHR aortae to NE were similar to those of the normotensive tissues. Schild plot data for alpha(1)-AR antagonists indicated that alpha(1)-AR subtypes mediating contraction of the aorta were homogeneous and had high affinities for bunazosin (pA(2) 9.4, alpha(1H) subtype) and WB 4101 (pA(2) 9.3) and a low affinity for 5-methylurapidil (pA(2) 7.7). In the femoral artery, because Schild plots for bunazosin had slopes of less than 1.0, there were alpha(1H) and alpha(1L) subtypes. Bunazosin, at 10(-9) M, which could mask the alpha(1H) subtype, yielded a Schild plot for bunazosin with a slope not different from unity and decreased the pA(2) value for bunazosin (pA(2) 9.4 vs. 8.5). Chlorethylclonidine inhibited the response of the aortic and femoral preparations to NE but did not change Schild plot data for 5-methylurapidil. It was suggested that in the rat femoral artery, alpha(1C) and alpha(1L) subtypes mediated the contractile response to NE. The alpha(1)-AR subtype in the aorta was essentially identical with the alpha(1H) subtype in the femoral artery. alpha(1)-AR subtypes mediating contraction in the SHR blood vessels were identical with those in the WKY tissues.