[Significance of endogenous nitric oxide production for the effect of nitrates and in septic shock].
The endothelial relaxation factor postulated by Furchgott has been identified as the endogenous nitro-vasodilatator nitric oxide (nitrogen monoxide, NO). NO is derived from L-arginine and plays an important role in the regulation of circulation. In man, too, inhibitors of NO synthesis like L-NG monomethylarginine (L-NMMA) led to hypertension as well as to reduction of local blood flow. In vivo inhibition of NO synthesis leads to amplification of the effect and of the duration of the effect of nitrates. L-arginine/NO metabolism has also been detected in nonvascular tissues, i.e. from lungs, gastrointestinal tract and urogenital tract. The discovery of inducible nitric-oxide synthase activity in vascular smooth muscle cells, able to produce a great amount of NO, represents another important recent development. Important stimuli for the induction of this NO-synthase are cytokines that play possibly an important clinical role in the context of endotoxemic shock. Research over the last ten years has demonstrated that the L-arginine/NO system represents a central biological regulatory mechanism that plays an important role under physiologic and pathophysiologic conditions not only for the circulation but also in other organs.
Moncada
S
S
Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
D000594:Amino Acid Oxidoreductases / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D009566:Nitrates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D012772:Shock, Septic / Q000503:physiopathology*
D009566:Nitrates; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases