EFFECT OF N-G-MONOMETHYL-L-ARGININE ON KININ-INDUCED VASODILATION IN THE HUMAN FOREARM

1 We compared effects of N-G-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor, on vasodilator responses to intra-arterial infusion of bradykinin and substance P in the human forearm. 2 Bradykinin (100 pmol min(-1)) increased forearm blood flow when infused into the brachial artery of eight healthy male volunteers, from 2.8 +/- 0.2 (mean +/- s.e. mean) to 9.3 +/- 1.0 ml min(-1) per 100 ml forearm volume. 3 Co-infusion of L-NMMA (2 mu mol min(-1) and 4 mu mol min(-1)) with bradykinin (100 pmol min(-1)) for 6 min produced respectively a 9 +/- 14% and 42 +/- 14% inhibition (compared with L-NMMA vehicle) in the response to bradykinin. 4 Substance P (1 pmol min(-1)) when infused into the brachial artery of a further eight male subjects increased forearm blood flow from 3.4 +/- 0.2 to 6.3 +/- 0.7 ml min(-1) 100 ml(-1). 5 Co-infusion of L-NMMA (2 mu mol min(-1) and 4 mu mol min(-1)) with substance P (1 pmol min(-1)) for 6 min produced respectively a 27 +/- 8% and 70 +/- 13% inhibition (compared with L-NMMA vehicle) in the response to substance P. 6 These results demonstrate that vasodilator responses to both bradykinin and substance P are mediated in part via the L-arginine/NO pathway. Bradykinin and substance P may be useful agonists with which to study endothelial function in this vascular bed.