PT - JOURNAL ARTICLE AU - C Baylis AU - S Masilamani AU - G Losonczy AU - L Samsell AU - P Harton AU - K Engels TI - 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. DP - 1995 Sep 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1135--1141 VI - 274 IP - 3 4099 - http://jpet.aspetjournals.org/content/274/3/1135.short 4100 - http://jpet.aspetjournals.org/content/274/3/1135.full SO - J Pharmacol Exp Ther1995 Sep 01; 274 AB - We have previously reported that acute systemic nitric oxide (NO) blockade in the conscious rat leads to increases in blood pressure and a profound renal vasoconstriction. In the present studies, we investigated the effect on renal vascular resistance of normalization of blood pressure (BP) during acute, i.v. NO blockade with nitro-L-arginine methyl ester (NAME). We found that two separate pharmacologic maneuvers which normalized BP after a transient period of hypertension, namely the NO donor sodium nitroprusside (SNP) or the calcium entry blocker verapamil (VER), did not reverse the increased renal vascular resistance (RVR) produced by acute NAME. In further studies, we prevented the transient 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 pressure, RVR was unchanged compared to control. When we used angiotensin II (AII) as an alternative method of producing acute increases in BP and RVR, we found that VER reversed both the hypertension and the renal vasoconstriction, despite exposure of the kidney to a transient increase in BP. These data suggest that acute, transient exposure of the kidney to an increased BP during NO inhibition produces a sustained increase in RVR that is not reversible with either SNP or VER. The urinary data suggest that the combination of NAME and VER have a synergistic effection the renal tubule to produce a massive natriuretic and diuretic response.