ALPHA-METHYLNORADRENALINE-INDUCED CONTRACTIONS IN RAT AORTA ARE MEDIATED VIA ALPHA(1D)-ADRENOCEPTORS

The subtype(s) of alpha-adrenoceptor-mediating contractions to alpha-m ethynoradrenaline in the rat aorta has been investigated by using alph a-adrenoceptor-selective competitive antagonists and the alpha(1)-adre noceptor selective agonist, phenylephrine, for comparison. alpha-Methy lnoradrenaline and phenylephrine elicited concentration-dependent cont ractions in the endothelium-denuded and endothelium-intact aortic ring s with similar potencies and maximal effects. alpha-Methylnoradrenalin e- and phenylephrine-induced contractions in endothelium-denuded aorti c rings were competitively antagonized by prazosin (pA(2) = 9.38 and 9 .13; respectively) and rauwolscine (pA(2) = 7.19 and 6.60, respectivel y). This confirms that there is an alpha(1)- and a non alpha(2)-adreno ceptor response to alpha-methylnoradrenaline in the rat aorta. The sub type selective alpha(1D)-adrenoceptor antagonist, BMY 7378, was found to antagonize contractions to alpha-metbylnoradrenaline and phenylephr ine competitively in endothelium-denuded and endothelium-intact aortic rings. The pA(2) values of BMY 7378 against alpha-methylnoradrenaline (8.39 and 8.41; endothelium-intact and endothelium-denuded, respectiv ely) and phenylephrine (8.64 and 8.76; endothelium-intact and endothel ium-denuded, respectively), are consistent with its published function al potency and clonal alpha(1d)-adrenoceptor binding affinity. In addi tion, contractions to alpha-methylnoradrenaline and phenylephrine in e ndothelium-denuded aortic rings, were potently inhibited by WE 4101 wi th pA(2) values of 9.75 and 9.25, respectively. The high pA(2) values for WE 4101 indicate that the alpha(1B)-adrenoceptor subtype does not seem to participate in alpha-methylnoradrenaline (and phenylephrine) i nduced contractions in this artery. These results suggest that the alp ha(1D)-subtype plays a determining role in rat aorta contractions indu ced by alpha-methylnoradrenaline.