Influence of nifedipine on functional responses in vivo initiated at alpha 2-adrenoceptors.
The pressor effects of intravenous B-HT 920 in pithed cats were sensitive to antagonism by yohimbine (1 mg/kg i.v.), but not by prazosin (1 mg/kg i.v.). In contrast, prazosin profoundly affected the vasoconstriction caused by intravenous (-)-phenylephrine, whereas yohimbine only slightly influenced this response. These results confirm and extend earlier observations which favor a distinct subclassification of vascular postsynaptic alpha-adrenoceptors into alpha 1- and alpha 2-subtypes. Vasoconstriction in pithed cats by B-HT 920 was markedly antagonized by low doses (30 and 100 micrograms/kg) of nifedipine in a noncompetitive manner. The hypertensive responses to (-)-phenylephrine were moderately attenuated in a competitive fashion. These findings are consistent with the concept that extracellular calcium ions are indispensable for linking vascular alpha 2-adrenoceptor activation to vasoconstriction in vivo. Nifedipine (up to 1 mg/kg i.v.) neither interfered with the tachycardia induced by electrical stimulation in pithed normotensive rats nor influenced the inhibitory effect of B-HT 920. Clonidine's (0.3 mg/kg i.p.) prolongation of the hexobarbitone-induced loss of the righting reflex in mice was unchanged after nifedipine administration (up to 1 mg/kg i.p.). The central hypotensive action of clonidine in anesthetized cats (1 microgram/kg via vertebral artery) and in anesthetized normotensive rats (3-30 micrograms/kg i.c.v.) was reduced by nifedipine (30 and 100 micrograms/kg i.v. or i.c.v.). The results show a differential influence of nifedipine on functional responses in vivo caused by stimulation of pre- and postsynaptic alpha 2-adrenoceptors. In contrast to its inability to inhibit alpha 2-adrenoceptor-mediated effects at presynaptic sites, this calcium entry blocker impairs postsynaptic alpha 2-adrenoceptor-induced responses.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051379:Mice; D009543:Nifedipine / 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; D015016:Yohimbine / Q000494:pharmacology
D011725:Pyridines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D009543:Nifedipine; D003000:Clonidine