NITRIC-OXIDE DOSE-RESPONSE STUDY IN THE ISOLATED-PERFUSED RAT-KIDNEY AFTER INHIBITION OF ENDOTHELIUM-DERIVED RELAXING FACTOR SYNTHESIS - THE ROLE OF SERUM-ALBUMIN

The dose-response relationship of steady-state nitric oxide (NO) admin istration on renal vascular resistance in isolated rat kidneys (IPRK) perfused at constant pressure was investigated after inhibition of NO synthesis with N-G-monomethyl-L-arginine (L-NMMA). To study the influe nce of biological thiols on renovascular NO effects, experiments were carried out with Krebs-Henseleit (KH) perfusate solutions alone, and i n combination with bovine serum albumin (KH-ALB). Steady-state adminis tration of NO by gassing the perfusate with 0 to 340 ppm NO led to gra ded decreases in renovascular tone. The minimal effective NO perfusate concentration in the absence of endogenous NO synthesis was about 6 t o 8 nM, whereas a near-maximal effect was observed with similar to 200 nM. The presence of albumin reduced the speed of onset of renal vasod ilation and the maximal effect at a given concentration of NO, After t ermination 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, po tent renal vasodilation was caused by a reaction of bovine serum album in (BSA) with oxides of nitrogen to form S-nitroso-BSA. Nitrosothiol l evels in the KH-ALB perfusate were found to be proportional to the con centration of NO administered. The above-mentioned findings, confirmed in identical experiments with diethylamine NONOate, a novel NO-libera ting substance, support the biological importance of S-nitrosothiols ( RS-NO) in the action and metabolism of endothelium-derived relaxing fa ctor (EDRF) in the IPRK.