Organic and inorganic calcium antagonists reduce vasoconstriction in vivo mediated by postsynaptic alpha 2-adrenoceptors.
The influence of various calcium antagonists and divalent metal cations on the pressor responses induced by the selective alpha 1-adrenoceptor agonist methoxamine and the selective alpha 2-adrenoceptor stimulating agent B-HT 920 (2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]-azepine) was studied in pithed rats. 1. The calcium antagonists verapamil, D 600 and nifedipine, when given intraarterially (i.a.) in doses up to 1 mg/kg did not influence the pressor effects of methoxamine. Only higher amounts of these calcium antagonistic drugs (1 - 3 mg/kg i.a.) somewhat reduced this pressor response. 2. The vasoconstriction due to B-HT 920, as reflected by the increase in diastolic pressure, was markedly inhibited by verapamil, D 600 and nifedipine in a dose-dependent manner. In low doses a parallel displacement to the right was observed, whereas in higher amounts the shift was non-parallel. 3. The divalent cations MN2+, Ni2+ and Co2+ (0.05 - 0.15 mmol/kg i.a.) hardly affected the pressor effect of methoxamine, whereas B-HT 920-induced vasoconstriction was highly sensitive to these metal ions. La3+ and Mg2+ were ineffective. 4. The calcium antagonists verapamil, D 600 and nifedipine displayed only minor affinities for [3H]prazosin (alpha 1) as well as [3H]clonidine (alpha 2) binding sites of rat brain membranes. 5. It is concluded that an influx of extracellular Ca2+ is necessary for the vasoconstriction in vivo initiated by stimulation of vascular postsynaptic alpha 2-adrenoceptors. On the other hand, vasopressor responses to alpha 1-adrenoceptor stimulation are not directly dependent on a transmembrane influx of calcium ions.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000037:antagonists & inhibitors*; D004347:Drug Interactions; D008297:Male; D008566:Membranes / Q000378:metabolism; D008670:Metals / Q000494:pharmacology*; D051381:Rats; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013569:Synapses / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D008670:Metals; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D002118:Calcium