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 et al., 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 Journal of pharmacology and experimental therapeutics, 273(2), 1995, pp. 855-862
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.