Local L-NG-monomethyl-arginine attenuates the vasodilator action of bradykinin in the human forearm.
1. Studies in animals indicate that bradykinin relaxes blood vessels directly through an action on smooth muscle and indirectly through the release of endothelium-derived mediators. Its precise mechanism of action in the human arterial circulation is not yet known. 2. In this study the effects of a specific inhibitor of nitric oxide synthase, L-NG-monomethyl-arginine (L-NMMA) and noradrenaline on the vasodilator responses to bradykinin were examined in the forearm arterial bed of healthy volunteers. Noradrenaline was used as a control for vasoconstriction by L-NMMA; glyceryl trinitrate (GTN) as a control vasodilator acting independently of the NO synthase enzyme. 3. L-NMMA (4 mumol min-1; 5 min) alone reduced resting forearm blood flow by 44% (P < 0.01; n = 6) confirming that nitric oxide plays an important role in regulating vascular tone. 4. Bradykinin (10 and 100 pmol min-1; 3 min each dose) and GTN (2 and 5 nmol min-1; 3 min each dose) increased forearm blood flow in a dose-dependent manner (percentage changes 171 +/- 17% and 398 +/- 35%, and 176 +/- 21% and 268 +/- 42%, respectively; n = 6). 5. The response to bradykinin, but not that to GTN, was attenuated by L-NMMA compared with noradrenaline (P < 0.05; n = 6), suggesting that bradykinin-induced vasodilatation in the forearm is mediated, at least in part, by stimulating release of nitric oxide.
Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, London.
K P
KP
O'Kane
D J
DJ
Webb
J G
JG
Collier
P J
PJ
Vallance
D000328:Adult; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D005996:Nitroglycerin; D001920:Bradykinin; D009638:Norepinephrine