N G-Methyl-l-arginine (L-NMA) and N G-nitro-l-arginine (L-NNA) inhibited NO-induced cGMP accumulation in porcine aortic endothelial cells with half-maximally effective concentrations of 15 and 3.4 μM, respectively. The effects of both compounds were reversible, but the L-NNA-induced inhibition was only reversed by wash-out in the presence of 1 mM l-arginine. In short-term incubations (45 s) of membrane fractions, L-NMA and L-NNA exhibited similar potencies to inhibit endothelial NO synthase, but L-NNA was markedly more potent than L-NMA after prolonged incubation periods (⩾ 3 min) due to induction of a pronounced, reversible enzyme inactivation.
