Reversible inactivation of endothelial nitric oxide synthase by N G‐nitro‐l‐arginine

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.

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