The inhibitory effect of newer calcium antagonists (nimodipine and PY-108-068) on vasoconstriction in vivo mediated by postsynaptic alpha 2-adrenoceptors.
In the pithed rat, stimulation of postsynaptic alpha 1 as well as alpha 2-adrenoceptors is known to cause vasoconstriction. The two newer nifedipine-related calcium antagonistic agents nimodipine and PY-108-068 proved potent inhibitors of pressor responses induced by the selective alpha 2-receptor agonist B-HT 920. The maximal pressor effect of B-HT 920 was significantly reduced, whereas the hypertensive effects brought about by selective postsynaptic alpha 1-adrenoceptor stimulation were, but slightly, impaired by nimodipine and PY-108-068 and the maximal increase in diastolic pressure was not affected by the calcium antagonists. Under beta-blockade and suppression of alpha 1-adrenoceptor-mediated vasoconstrictor effects by prazosin, the resulting alpha 2-adrenoceptor-induced vasopressor response to (-)-norepinephrine proved also very sensitive towards the inhibitory action of nimodipine and PY-108-068. In comparison with nifedipine, PY-108-068 was 3.9 and nimodipine 5.1-times more potent with respect to reducing vasopressor responses of B-HT 920.
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009539:Nicotinic Acids / Q000494:pharmacology*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology*; D009553:Nimodipine; D009638:Norepinephrine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*
D001381:Azepines; D002121:Calcium Channel Blockers; D009539:Nicotinic Acids; D011725:Pyridines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D009553:Nimodipine; C024763:talipexole; D008729:Methoxamine; D009543:Nifedipine; C034600:darodipine; D009638:Norepinephrine