REVERSAL BY THE CALCIUM-ANTAGONIST NISOLDIPINE OF NOREPINEPHRINE-INDUCED REDUCTION OF GFR - EVIDENCE FOR PREFERENTIAL ANTAGONISM OF PREGLOMERULAR VASOCONSTRICTION

Abstract

The organic Ca2+ antagonist diltiazem augments the glomerular filtration rate (GFR) of the isolated perfused rat kidney during norepinephrine (NE)- induced vasoconstriction was demonstrated. These studies, did not elucidate the precise mechanism or site of action responsible for this effect. Nisoldipine (NIS) interacted with the same Ca2 channels as diltiazem but differed in its physicochemical properties, binding characteristics and tissue specificity. The effect of NIS using an identical model were examined. Renal perfusate flow and GFR were assessed in the isolated perfused rat kidney under conditions of constant renal perfusion pressure (100 mm Hg). NIS (10-7 M) completely reversed the NE-induced reduction in GFR but was significantly less effective in augmenting renal perfusate flow. In an additional series of experiments, filtration pressure was estimated during these manipulations by monitoring ureteral pressure during ureteral occlusion (stop-flow pressure). The NE-induced decrease in GFR was accompanied by a reduction in stop-flow pressure, which was abolished by the subsequent administration of NIS. Nisoldipine preferentially attenuated NE-induced constriction of preglomerular resistance vessels but was less effective in reversing the effects of NE on postglomerular arterioles. Separate postreceptor mechanisms apparently mediate the activation of pre- and postglomerular vessels by NE.