Nitric oxide dose-response study in the isolated perfused rat kidney after inhibition of endothelium-derived relaxing factor synthesis: the role of serum albumin

MA Kaufmann, I Castelli, H Pargger and LJ Drop

Beecher Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, USA.

The dose-response relationship of steady-state nitric oxide (NO) administration on renal vascular resistance in isolated rat kidneys (IPRK) perfused at constant pressure was investigated after inhibition of NO synthesis with NG-monomethyl-L-arginine (L-NMMA). To study the influence of biological thiols on renovascular NO effects, experiments were carried out with Krebs-Henseleit (KH) perfusate solutions alone, and in combination with bovine serum albumin (KH-ALB). Steady-state administration of NO by gassing the perfusate with 0 to 340 ppm NO led to graded decreases in renovascular tone. The minimal effective NO perfusate concentration in the absence of endogenous NO synthesis was about 6 to 8 nM, whereas a near-maximal effect was observed with approximately 200 nM. The presence of albumin reduced the speed of onset of renal vasodilation and the maximal effect at a given concentration of NO. After termination of NO administration, NO-induced vasodilation persisted in KH-ALB perfused kidneys for 30 min, whereas KH-perfused kidneys showed a rapid reconstriction. These findings suggest that the prolonged, potent renal vasodilation was caused by a reaction of bovine serum albumin (BSA) with oxides of nitrogen to form S-nitroso-BSA. Nitrosothiol levels in the KH-ALB perfusate were found to be proportional to the concentration of NO administered. The above- mentioned findings, confirmed in identical experiments with diethylamine NONOate, a novel NO-liberating substance, support the biological importance of S-nitrosothiols (RS-NO) in the action and metabolism of endothelium-derived relaxing factor (EDRF) in the IPRK.

Volume 273, Issue 2, pp. 855-862, 05/01/1995
Copyright © 1995 by American Society for Pharmacology and Experimental Therapeutics

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