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/p H changes are associated with organ ischaemia; therefore, we studied t he possibility that pH changes could alter the pharmacological effects of the calcium channel blocker nifedipine on rat tail artery contract ed 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 con tinued with a nominally calcium-free PSS made acidotic (pH7.20), alkal otic (pH 7.67) or unaltered (control), After equilibration, the perfus ion pressure (PP) responses to increasing concentrations of calcium in the presence of NA (3.0 mu mol/L) or potassium (100 mmol/L) with nife dipine or its vehicle were recorded, 3, The calcium sensitivity of pot assium-or NA-stimulated rat tail arteries was reduced during acidosis, as was the maximum PP in potassium-but not NA-stimulated tissues. Alk alosis: reduced the calcium sensitivity in potassium-but not NA-stimul ated contraction and had no effect on maximum PP, 4, The inhibitory ef fect of nifedipine (0.6 mu mol/L) on contraction was enhanced during a cidosis 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 t he vascular contractility profile in a manner dependent on the excitat ion-contraction coupling mode. The calcium antagonistic effect of nife dipine is pH dependent and it is suggested that pH changes associated with ischaemic conditions may alter the therapeutic profile of nifedip ine.