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.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D001381:Azepines; C024763:talipexole; C035813:B-HT 958; D009543:Nifedipine