Alpha 1- and alpha 2-adrenoceptor-mediated pressor responses: are they differentiated by calcium antagonists or by functional antagonism?
We investigated the effect of cardiovascular depression on the pressor responses to the alpha 1-adrenoceptor selective agonist methoxamine, and the alpha 2-adrenoceptor selective agonist B-HT 920 in anesthetized ganglion-blocked rats. The calcium channel blocking drug nifedipine preferentially inhibited the effect of B-HT 920, as has been reported by other authors. Lowering the starting blood pressure by hemorrhage, by nitroprusside infusion, or by additional pentobarbitone also preferentially inhibited the pressor effect of B-HT 920. These selective effects of vascular depression on B-HT 920 are consistent with predicted interactions between functional antagonists and a partial (low-efficacy) agonist. This was tested in part by reducing the maximum effect of methoxamine by phenoxybenzamine treatment. Under these conditions, methoxamine behaved like B-HT 920 in that it was sensitive to inhibition by nitroprusside infusion. By analogy, the vasodepressive effect of calcium channel blocking drugs could be responsible for the preferential inhibition of the vasoconstrictor responses to alpha 2-adrenoceptor agonists. It is concluded that a differential reliance on influx of extracellular Ca2+ by alpha 1- and alpha 2-adrenoceptors may not be the only explanation of the selective effect of calcium channel blocking drugs.
Lew
M J
MJ
Angus
J A
JA
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000502:physiology; D006470:Hemorrhage / Q000503:physiopathology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D001381:Azepines; D002121:Calcium Channel Blockers; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D009599:Nitroprusside; C024763:talipexole; D008729:Methoxamine; D010424:Pentobarbital; D009543:Nifedipine; D002118:Calcium