Lack of relationship between intrinsic activity and susceptibility of pressor responses to blockade by nifedipine among the alpha 2-adrenoceptor agonists B-HT 920 and B-HT 958.

Following i.v. bolus injections into pithed normotensive rats, the maximal diastolic pressor responses to B-HT 920 and B-HT 958 amounted to 115 and 35 mm Hg, respectively. Prazosin (0.1 mg/kg, i.v., -15 min) was without effect on the log dose-pressor effect curve of B-HT 958, whereas yohimbine (1 mg/kg, i.v., -15 min) shifted this curve about 30-fold to the right, showing the exclusive participation of alpha 2-adrenoceptors in the vasoconstrictor response to B-HT 958. In doses of 10 and 30 mg/kg, B-HT 958 displaced the log dose-vasoconstrictor effect curve of B-HT 920 approximately 6- and 30-fold, respectively, to the right, illustrating the partial agonism of B-HT 958 at postjunctional vascular alpha 2-adrenoceptors. Despite the marked difference in intrinsic activity of B-HT 920 and B-HT 958, the calcium entry blocker nifedipine exhibited a comparable inhibitory action on the vasopressor responses to both agonists. This finding indicates that partial and full agonism at vascular alpha 2-adrenoceptors are not related to the susceptibility of the initiated pressor response to inhibition by calcium entry blockade.