Effects of nitric oxide synthase blockers on renal function.
Three isoforms of nitric oxide synthase (NOS) [neuronal NOS (bNOS), inducible NOS (iNOS) and endothelial NOS (eNOS)] are expressed in the kidney. The use of pharmacological inhibitors of these enzymes has been a major experimental tool to determine the role of nitric oxide (NO) in renal physiology and pathophysiology. Studies performed in both human and experimental animals demonstrate that NOS blockade increases renal vascular resistances and decreases the glomerular ultrafiltration coefficient. These studies also support the presence of an important interaction between NO, angiotensin and renal nerves in the control of renal function. Renal iNOS activity is significantly increased in various pathophysiological conditions including autoimmune tubulointerstitial nephritis and sepsis. Interestingly, recent evidence suggests that high NO levels secondary to increased iNOS activity may inhibit eNOS activity and through this mechanism lead to renal vasoconstriction and reductions in glomerular filtration rate. The use of NOS blockers has generated a great deal of information on the role of NO in the control of renal function and has also allowed us to begin to understand the high level of complexity of this system.
Gabbai
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Division of Nephrology/Hypertension, VA San Diego Healthcare System and University California San Diego, La Jolla, CA 92093, USA.
D000818:Animals; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D009395:Nephritis, Interstitial / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D018805:Sepsis / Q000503:physiopathology; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D019323:omega-N-Methylarginine; C496320:NOS1 protein, human; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III