TY - JOUR T1 - Comparison of the inhibitory potencies of N(G)-methyl-, N(G)-nitro- and N(G)-amino-L-arginine on EDRF function in the rat: evidence for continuous basal EDRF release. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1208 LP - 1215 VL - 257 IS - 3 AU - H M Vargas AU - J M Cuevas AU - L J Ignarro AU - G Chaudhuri Y1 - 1991/06/01 UR - http://jpet.aspetjournals.org/content/257/3/1208.abstract N2 - The relative potencies of the argininolytic agents NG-methyl-L-arginine (L-NMA), NG-nitro-L-arginine (L-NNA) and NG-amino-L-arginine (L-NAA) were assayed by their inhibitory effect on both basal and stimulated release of endothelium-derived NO in vitro and in vivo. Basal NO release was indirectly assessed by the ability of the analogs to contract phenylephrine-preconstricted rat aortic rings and their ability to produce a hypertensive response in awake, unanesthetized normotensive rats. In aortic rings, the three analogs induced vasocontraction and inhibited the vasorelaxation mediated by ACh-stimulated endothelial NO release. In this latter assay, L-NNA was 30 times more potent than either L-NMA or L-NAA. In free-moving rats, the agents caused dose-dependent increases in arterial pressure due to the blockade of endogenous NO formation. Dose-response analysis indicated that L-NNA was 87 and 230 times more potent than L-NMA and L-NAA, respectively. Pretreatment with L-NNA was also found to selectively inhibit, but not abolish, the depressor effects of acetylcholine in unanesthetized and phenylephrine- or vasopressin-infused normotensive-pithed rats. These studies indicate that L-NNA is a potent antagonist of endothelium-derived relaxing factor formation in vitro and in vivo. The contractile and hypertensive effects of the argininolytic agents clearly demonstrates that a continuous basal release of endothelium-derived relaxing factor/NO occurs in both isolated vascular rings and whole animals. ER -