Effects of acidosis or alkalosis on the actions of nifedipine on excitation-contraction coupling in the rat tail artery

1, The clinical success of calcium channel blockers in the management of organ ischaemia is less than theoretically anticipated, Blood gas/pH changes are associated with organ ischaemia; therefore, we studied the possibility that pH changes could alter the pharmacological effects of the calcium channel blocker nifedipine on rat tail artery contracted by either noradrenaline (NA) or potassium, 2, Segments (22.5cm) of the proximal third of the male Sprague-Dawley rat tail ventral artery were initially bathed and perfused with a physiological salt solution (PSS; pH7.48) for 25-30min, after which time bathing/perfusion was continued with a nominally calcium-free PSS made acidotic (pH7.20), alkalotic (pH 7.67) or unaltered (control), After equilibration, the perfusion pressure (PP) responses to increasing concentrations of calcium in the presence of NA (3.0 mu mol/L) or potassium (100 mmol/L) with nifedipine or its vehicle were recorded, 3, The calcium sensitivity of potassium-or NA-stimulated rat tail arteries was reduced during acidosis, as was the maximum PP in potassium-but not NA-stimulated tissues. Alkalosis: reduced the calcium sensitivity in potassium-but not NA-stimulated contraction and had no effect on maximum PP, 4, The inhibitory effect of nifedipine (0.6 mu mol/L) on contraction was enhanced during acidosis in either NA-or potassium-stimulated arteries and also during alkalosis in NA-treated arteries, although it had little effect during normal conditions, 5, The results indicate that changes in pH alter the vascular contractility profile in a manner dependent on the excitation-contraction coupling mode. The calcium antagonistic effect of nifedipine is pH dependent and it is suggested that pH changes associated with ischaemic conditions may alter the therapeutic profile of nifedipine.