Effect of N^G‐monomethyl‐L‐arginine on kinin‐induced vasodilation in the human forearm.

1. We compared effects of NG‐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 mumol min‐1 and 4 mumol 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 mumol min‐1 and 4 mumol 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. 1994 The British Pharmacological Society