Nitric oxide synthesised from L-arginine mediates endothelium dependent dilatation in human veins in vivo.
Endothelium derived relaxing factor (EDRF) has been identified as nitric oxide, synthesised from the amino acid L-arginine, a process which is inhibited by the L-arginine analogue NG-monomethyl L-arginine (L-NMMA). We have studied the effect of local infusions of L-NMMA on venous reactivity in healthy volunteers. Studies were performed using the veins on the back of the hand. The diameter of a single dorsal hand vein was measured in healthy subjects who had taken 600 mg of aspirin 30 min before the experiment. Changes in diameter were recorded during local infusions of noradrenaline, bradykinin, acetylcholine, glyceryl trinitrate, L- and D-arginine and its NG-monomethyl derivatives. L-NMMA (100 nmol.min-1) stereospecifically inhibited vasodilatation induced by acetylcholine and bradykinin (p less than 0.02) but not that induced by the endothelium independent vasodilator glyceryl trinitrate. L-NMMA (100 nmol.min-1) potentiated the venoconstrictor effect of a high dose of acetylcholine (100 nmol.min-1) without affecting the action of noradrenaline and without having a direct venoconstrictor effect in doses up to 10 mumol.min-1. These results show that the venous effects of certain vasodilators in man are mediated through the release of nitric oxide (EDRF) synthesised from L-arginine. They also highlight differences in basal and stimulated production of nitric oxide between arteries and veins.
Vallance
P
P
Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, London, United Kingdom.
Collier
J
J
Moncada
S
S
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D006225:Hand / Q000098:blood supply*; D006801:Humans; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014680:Veins / Q000187:drug effects / Q000502:physiology; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine