Action of oxmetidine on the rabbit aorta: Comparison with some calcium entry blockers and nitroglycerin

Abstract

The novel histamine H2 receptor antagonist, oxmetidine, was tested on isolated rabbit aorta for its activity on calcium ion transport and/or utilization suggested from previous experiments. Its effect was compared with that of some "classical" calcium entry blockers (verapamil, D-600 and nifedipine) and of nitroglycerin which acts predominantly on the intracellular calcium. The effect of all these compounds was evaluated against the contraction elicited by KCl, angiotensin and noradrenaline acting by different spasmogenic mechanisms. Oxmetidine was found to antagonize to approximately the same extent the effect of the three stimulatory substances: however concentrations required for this effect were from 10 to 100 times as high as those required to inhibit histamine H2 receptors. Nitroglycerin behaved quite similarly but was approximately 10.000 times more potent than oxmetidine. Verapamil and D-600 (which were virtually identical) were always more potent (about 10 times) than oxmetidine but less efficacious on the angiotensin-induced contraction. Finally nifedipine was the most active compound on the KCl induced contraction but was almost ineffective against angiotensin. It is concluded that oxmetidine, though with a still unclear mechanism, possesses a weak but definite inhibitory effect on the availability of the intracellular calcium resembling the effect of nitroglycerin. Whether or not an action on the influx of calcium is also present cannot be surely established as long as calcium fluxes are not measured. Differences in the behaviour of the "classical" calcium entry blockers suggest that each of them possesses, together with the main well recognized effect, additional effects responsible for apparently surprising results obtained against different spasmogenic compounds.