Differential inhibition by N^G‐monomethyl‐l‐arginine of vasodilator effects of acetylcholine and methacholine in human forearm vasculature

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. 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. Co‐infusion of l‐NMMA (4 μmol 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). 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. Co‐infusion of l‐NMMA (4 μmol 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 μmol min⁻¹) with methacholine (1.5 nmol min⁻¹) did not significantly inhibit the vasodilator response (n = 7). These results suggest that, in human forearm vasculature, methacholine acts predominantly through mechanisms other than the l‐arginine/nitric oxide pathway. 1993 British Pharmacological Society