Organic and inorganic calcium antagonists reduce vasoconstriction in vivo mediated by postsynaptic alpha...

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.