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) 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.
Kaufmann
M A
MA
Beecher Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Castelli
I
I
Pargger
H
H
Drop
L J
LJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004048:Diethylamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000502:physiology*; D012977:Sodium Nitrite / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine
D004048:Diethylamines; D009603:Nitroso Compounds; D012709:Serum Albumin; D013438:Sulfhydryl Compounds; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; C034281:diethylamine; D012977:Sodium Nitrite