Reversal by the calcium antagonist nisoldipine of norepinephrine-induced reduction of GFR: evidence for preferential antagonism of preglomerular vasoconstriction.
We have demonstrated previously that the organic Ca++ antagonist diltiazem augments the glomerular filtration rate (GFR) of the isolated perfused rat kidney during norepinephrine (NE) - induced vasoconstriction. These earlier studies, however, did not elucidate the precise mechanism or site of action responsible for this effect. Nisoldipine (NIS) interacts with the same Ca+2 channels as diltiazem but differs in its physicochemical properties, binding characteristics and tissue specificity. We examined, therefore, the effects of NIS using an identical model. Renal perfusate flow and GRF 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 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. Thus, nisoldipine preferentially attenuated NE-induced constriction of preglomerular resistance vessels but was less effective in reversing the effects of NE on postglomerular arterioles. These findings indicate that separate postreceptor mechanisms mediate the activation of pre- and postglomerular vessels by NE.
D000818:Animals; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015737:Nisoldipine; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010477:Perfusion; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D015737:Nisoldipine; D009543:Nifedipine; D009638:Norepinephrine; D010646:Phentolamine