alpha-methylnoradrenaline-induced contractions in rat aorta are mediated via alpha(1D)-adrenoceptors

The subtype(s) of alpha-adrenoceptor-mediating contractions to alpha-methynoradrenaline in the rat aorta has been investigated by using alpha-adrenoceptor-selective competitive antagonists and the alpha(1)-adrenoceptor selective agonist, phenylephrine, for comparison. alpha-Methylnoradrenaline and phenylephrine elicited concentration-dependent contractions in the endothelium-denuded and endothelium-intact aortic rings with similar potencies and maximal effects. alpha-Methylnoradrenaline- and phenylephrine-induced contractions in endothelium-denuded aortic rings were competitively antagonized by prazosin (pA(2) = 9.38 and 9.13; respectively) and rauwolscine (pA(2) = 7.19 and 6.60, respectively). This confirms that there is an alpha(1)- and a non alpha(2)-adrenoceptor response to alpha-methylnoradrenaline in the rat aorta. The subtype selective alpha(1D)-adrenoceptor antagonist, BMY 7378, was found to antagonize contractions to alpha-metbylnoradrenaline and phenylephrine 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, respectively) and phenylephrine (8.64 and 8.76; endothelium-intact and endothelium-denuded, respectively), are consistent with its published functional potency and clonal alpha(1d)-adrenoceptor binding affinity. In addition, contractions to alpha-methylnoradrenaline and phenylephrine in endothelium-denuded aortic rings, were potently inhibited by WE 4101 with 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) induced contractions in this artery. These results suggest that the alpha(1D)-subtype plays a determining role in rat aorta contractions induced by alpha-methylnoradrenaline.