Physiology and pathophysiology of nitric oxide in chronic renal disease.
Nitric oxide (NO), an L-arginine derivative, exerts a variety of renal and extrarenal physiological and pathophysiological effects. NO is generated by three isoforms of nitric oxide synthases (NOS): two acutely responsive, constitutive isoforms, neuronal NOS (nNOS) and endothelial NOS (ecNOS), and the slower, more persistent, inducible NOS (iNOS). NO regulates glomerular ultrafiltration; tubular reabsorption, and intrarenal renin secretion. A number of recent studies, most of them in the experimental model of renal mass reduction (RMR) in rats, have raised the hypothesis that an impaired NO synthetic pathway could have a key role in mediating the complex renal hemodynamic and nonhemodynamic disorders associated with the progression of renal disease. Thus, kidneys from rats with RMR produce less NO than normal rats, and NO generation negatively correlates with markers of renal damage. The abnormality is due to a defect in iNOS in the kidney. Data are also available showing that drugs capable of enhancing renal NO activity may be renoprotective in a variety of experimental renal diseases, particularly those characterized by derangements of glomerular hemodynamics. Fewer studies are available in humans and these have shown less than conclusive results.
Noris
M
M
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Remuzzi
G
G
D000818:Animals; D002384:Catalysis; D019332:Endothelin-1 / Q000502:physiology; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology; D006439:Hemodynamics; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D009392:Nephrectomy; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats
D019332:Endothelin-1; D006133:Growth Substances; D007527:Isoenzymes; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase