Influence of pH changes on the actions of verapamil on vascular excitation-contraction coupling

Abstract

We have previously shown that pH changes alter the cardiovascular responses to verapamil in rat, in vivo and in isolated rat heart. The current study investigated the influence of pH changes on the actions of verapamil on potassium- or noradrenaline-stimulated contraction in rat tail arteries. The proximal 2-2.5 cm of ventral tail artery was bathed in and perfused initially (20–25 min) with physiological salt solution (pH 7.4) which was later made calcium-free at pH 7.4 (control), pH 7.2 (acidosis) or pH 7.67 (alkalosis). After equilibration each artery was exposed to verapamil following which the contractile responses to increasing concentrations of calcium were recorded. The patterns of responses in noradrenaline- or potassium-stimulated arteries were different. In normal conditions, the vasodilator effect of verapamil was predominant in potassium-stimulated arteries but less in the noradrenaline-stimulated preparations. With pH changes the effect of verapamil was enhanced more in noradrenaline- than in potassium-stimulated arteries. It is postulated that pathology-induced changes in the character of calcium channels could alter the effect of calcium channel blockers.