Abstract

To evaluate the contribution of l arginine as a precursor of the endothelium-derived relaxing factor (EDRF) on vascular cyclic GMP formation, we examined the effects of lNG-monomethyl arginine (lNMMA), and analog of larginine, on basal and acetylcholine (ACh)-, sodium nitroprusside (SNP)- and atrial natriuretic peptide (ANP)-induced cyclic GMP formations in rat mesenteric arteries. The mesenteric arteries were perfused with Krebs-Henseleit solution containing 0.2 mM isobutyl methyl xanthine. The effluents from the arteries were collected before and after infusions of graded doses of ACh, SNP or ANP in the absence or presence of 100 µM lNMMA, and the levels of cyclic GMP were measured. Basal and ACh-induced cyclic GMP formations in the mesenteric arteries were significantly inhibited in the presence of lNMMA, whereas a concomitant infusion of 300 µM larginine restored the inhibition of basal as well as ACh-induced cyclic GMP formations. lNMMA did not affect SNP- and ANP-stimulated cyclic GMP formations, respectively. These results suggest that larginine is necessary for not only the stimulated cyclic GMP formation but also the basal cyclic GMP formation in the mesenteric arteries, whereas the SNP- and ANP-stimulated cyclic GMP formations in the arteries are independent of larginine.

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