BLOOD-PRESSURE (BP) AND RENAL VASOCONSTRICTOR RESPONSES TO ACUTE BLOCKADE OF NITRIC-OXIDE - PERSISTENCE OF RENAL VASOCONSTRICTION DESPITE NORMALIZATION OF BP WITH EITHER VERAPAMIL OR SODIUM-NITROPRUSSIDE

We have previously reported that acute systemic nitric oxide (NO) bloc kade in the conscious rat leads to increases in blood pressure and a p rofound renal vasoconstriction. In the present studies, we investigate d the effect on renal vascular resistance of normalization of blood pr essure (BP) during acute, i.v. NO blockade with nitro-L-arginine methy l ester (NAME). We found that two separate pharmacologic maneuvers whi ch normalized BP after a transient period of hypertension, namely the NO donor sodium nitroprusside (SNP) or the calcium entry blocker verap amil (VER), did not reverse the increased renal vascular resistance (R VR) produced by acute NAME. In further studies, we prevented the trans ient increase in BP with the same combination of NAME and VER but with simultaneous administration of the drugs and in this situation, where the kidney was never exposed to a transient rise in renal perfusion p ressure, RVR was unchanged compared to control. When we used angiotens in II (AII) as an alternative method of producing acute increases in B P and RVR, we found that VER reversed both the hypertension and the re nal vasoconstriction, despite exposure of the kidney to a transient in crease in BP. These data suggest that acute, transient exposure of the kidney to an increased BP during NO inhibition produces a sustained i ncrease in RVR that is not reversible with either SNP or VER. The urin ary data suggest that the combination of NAME and VER have a synergist ic effect on the renal tubule to produce a massive natriuretic and diu retic response.