LOCAL L-N-G-MONOMETHYL-ARGININE ATTENUATES THE VASODILATOR ACTION OF BRADYKININ IN THE HUMAN FOREARM

1 Studies in animals indicate that bradykinin relaxes blood vessels di rectly through an action on smooth muscle and indirectly through the r elease of endothelium-derived mediators. Its precise mechanism of acti on in the human arterial circulation is not yet known. 2 In this study the effects of a specific inhibitor of nitric oxide synthase, L-N-G-m onomethyl-arginine (L-NMMA) and noradrenaline on the vasodilator respo nses to bradykinin were examined in the forearm arterial bed of health y 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 mu mol 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 v ascular 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 bloo d 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-N MMA compared with noradrenaline (P < 0.05; n = 6), suggesting that bra dykinin-induced vasodilatation in the forearm is mediated, at least in part, by stimulating release of nitric oxide.