DIFFERENTIAL INHIBITION BY N(G)-MONOMETHYL-L-ARGININE OF VASODILATOR EFFECTS OF ACETYLCHOLINE AND METHACHOLINE IN HUMAN FOREARM VASCULATURE

1 We compared the effects of N(G)-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor, on vasodilatation produced by acetylcholine and methacholine in human forearm vasculature. 2 Acetylcholine (83 nmol min-1) infused into the brachial artery of 8 healthy volunteers caused a submaximal increase in forearm blood flow, measured by venous occlusion plethysmography, from 3.3 +/- 0.5 (mean +/- s.e.mean) to 13.3 +/- 1.7 ml min-1 100 ml-1. 3 Co-infusion of L-NMMA (4 mumol min-1)with acetylcholine (83 nmol min-1) over 6 min resulted in a 58% +/- 12% fall in the response to acetylcholine whereas during co-infusion of saline over the same time period in the same subjects (n = 8) on a different day the response to acetylcholine fell by only 9% +/- 17% (P<0.01). 4 Methacholine (1.5 and 15 nmol min-1) increased forearm blood flow from 2.5 +/- 0.4 to 5.9 +/- 0.9 and from 3.2 +/- 0.4 to 17.0 +/- 1.9 ml min-1 100 ml-1 respectively. 5 Co-infusion of L-NMMA (4 mumol min-1) had no significant effect on the response to methacholine (1.5 or 15 nmol min-1) when compared with saline control (n = 8). Co-infusion of a higher dose of L-NMMA (8 mumol min-1) with methacholine (1.5 nmol min-1) did not significantly inhibit the vasodilator response (n = 7). 6 These results suggest that, in human forearm vasculature, methacholine acts predominantly through mechanisms other than the L-arginine/nitric oxide pathway.