Nitric oxide in chronic renal failure.
Endothelium-derived nitric oxide (NO) is critically involved in the regulation of a wide variety of vascular functions. It had been hypothesized that a deficiency of vascular NO might be involved in the accelerated atherosclerosis and dramatic cardiovascular mortality observed in patients with chronic renal failure. At present it is difficult to measure authentic NO in vivo. An alternative is to study NO by its effect on vascular tone by using the forearm blood flow technique. In this way, studies demonstrated an unimpaired availability of NO under baseline conditions but a profound reduction of agonist-induced endothelium-dependent vasodilatation in uremic patients. Further investigation showed that the latter phenomenon is mainly attributable to a reduced availability of vascular NO upon agonist stimulation, while the NO-independent mechanism(s) appear(s) to be intact in this setting. Explanations for this finding include an uncoupling of NO synthase induced by cofactor deficiency, and/or a reduced NO availability caused by high levels of oxidative stress. Recent data suggest only a minor role for cytochrome-P450 2C9-dependent pathways in this context. Future studies have to show which mechanisms are most relevant, and whether they are sensitive to therapeutic intervention.
Passauer
Jens
J
Division of Nephrology, Department of Medicine, University Hospital Carl Gustav Carus, Dresden, Germany. passauer@rcs.urz.tu-dresden.de
Pistrosch
Frank
F
Büssemaker
Eckhart
E
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D014664:Vasodilation
D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III