A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation.
1. The role of L-arginine in the basal and stimulated generation of nitric oxide (NO) for endothelium-dependent relaxation was studied by use of NG-monomethyl L-arginine (L-NMMA), a specific inhibitor of this pathway. 2. L-Arginine (10-100 microM), but not D-arginine (100 microM), induced small but significant endothelium-dependent relaxations of rings of rabbit aorta. In contrast, L-NMMA (1-300 microM) produced small, endothelium-dependent contractions, while its enantiomer NG-monomethyl-D-arginine (D-NMMA; 100 microM) had no effect. 3. L-NMMA (1-300 microM) inhibited endothelium-dependent relaxations induced by acetylcholine (ACh), the calcium ionophore A23187, substance P or L-arginine without affecting the endothelium-independent relaxations induced by glyceryl trinitrate or sodium nitroprusside. 4. The inhibition of endothelium-dependent relaxation by L-NMMA (30 microM) was reversed by L-arginine (3-300 microM) but not by D-arginine (300 microM) or a number of close analogues (100 microM). 5. The release of NO induced by ACh from perfused segments of rabbit aorta was also inhibited by L-NMMA (3-300 microM), but not by D-NMMA (100 microM) and this effect of L-NMMA was reversed by L-arginine (3-300 microM). 6. These results support the proposal that L-arginine is the physiological precursor for the basal and stimulated generation of NO for endothelium-dependent relaxation.
Rees
D D
DD
Wellcome Research Laboratories, Beckenham, Kent.
Palmer
R M
RM
Hodson
H F
HF
Moncada
S
S
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011817:Rabbits; D013237:Stereoisomerism; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine