HETEROGENEITY OF ALPHA(1)-ADRENOCEPTOR SUBTYPES INVOLVED IN ADRENERGIC CONTRACTIONS OF DOG-BLOOD VESSELS

1 We determined the alpha(1),-adrenoceptor subtypes involved in adrene rgic contractions of eight different blood vessels isolated from the d og. 2 Noradrenaline produced concentration-dependent contractions in a ll the blood vessels tested, which were competitively inhibited by pra zosin, WB4101, HV723 and 5-methylurapidil. However, there was consider able difference between the vessels with regard to the pK(B) values fo r all the antagonists. The alpha(1)-adrenoceptors of dog vertebral and carotid arteries had high affinity for prazosin (pK(B)>9.0) but low a ffinity for WB4101 (<8.5), 5-methylurapidil (<7.5) and HV723 (<less th an or equal to 8.5). By contrast, HV723 had higher affinity (>9.0) tha n prazosin (<8.3), WB4101 (<8.7) and 5-methylurapidil (<8.2) in the po rtal vein, mesenteric artery and vein, and renal artery. In the femora l artery and vein, however, the four antagonists showed pK(B) values i n the range 8.0-8.7. 3 Chloroethylclonidine (10 mu M) produced a remar kable reduction of the contractile responses to noradrenaline in the v ertebral and carotid arteries as compared with those. in the other ves sels. Nifedipine inhibited the responses to noradrenaline in all the t issues tested, and had marked effects in the portal vein. 4 Sympatheti c adrenergic contractions induced by transmural electrical stimulation were also inhibited by prazosin and HV723 at different potencies amon g tissues. The relative potencies of both the antagonists paralleled t he relationship in inhibiting the responses to exogenous noradrenaline in each vessel. 5 According to recent alpha(1)-adrenoceptor subclassi fication, the present results suggest that the contractions of blood v essels induced by endogenous and exogenous noradrenaline are mediated through different alpha(1)-adrenoceptor subtypes heterogeneously distr ibuted in each vessel; presumably, the alpha(1B) subtype in the caroti d and vertebral arteries, the alpha(1N) subtype in the visceral region and the alpha(1L) subtype in the femoral region. Regionally different expression of alpha(1)-adrenoceptor subtypes may be in part associate d with he regional heterogeneity of sympathetic responses in the blood vessels.