1. Using a myograph to measure isometric tension, we have looked at the action of NG-monomethyl-l-arginine on the endothelium-dependent relaxation of human subcutaneous resistance arteries.
2. NG-Monomethyl-l-arginine, the novel inhibitor of endothelium-derived relaxing factor synthesis, caused concentration-dependent but only partial inhibition of maximal relaxation induced by acetylcholine in human subcutaneous resistance arteries.
3. The inhibitory action of NG-monomethyl-l-arginine on acetylcholine-induced maximal relaxation was partially reversed by incubation of the arteries in equimolar concentrations of l-arginine and NG-monomethyl-l-arginine. Subsequent incubation in l-arginine led to further reversal, but this was no greater than with incubation in physiological saline.
4. A component of acetylcholine-induced relaxation was sensitive to indomethacin, suggesting that this response is mediated by prostanoids as well as by endothelium-derived relaxing factor.
5. NG-Monomethyl-l-arginine did not increase the tension of resting human subcutaneous resistance arteries. NG-Monomethyl-l-arginine did enhance the contractile response to noradrenaline, possibly due to inhibition of release of endothelium-derived relaxing factor resulting from stimulation of α2-adrenoreceptors on the endothelial cells.
The inhibitory action of relaxing-factor preparations on the myofibrillar adenosine triphosphatase