Vasomotor responses of canine coronary arterial rings to NG-monomethyl- L-arginine and N omega nitro L-arginine methyl ester

MJ Winn, NK Asante and DD Ku

Department of Pharmacology, University of Alabama, Birmingham.

The actions of NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro L- arginine methyl ester (L-NAME) on canine coronary arterial rings were compared with effects on rat aortic rings. After incubation of rat aortic rings with indomethacin (5 x 10(-6) M) and preconstriction with phenylephrine (10(-7) M), L-NMMA (2.5 x 10(-4) M) caused an increase in tension when endothelium remained intact (+1.1 +/- 0.2 g). L-NMMA had no effect when endothelium was absent. After incubation of canine coronary arterial rings with indomethacin and preconstriction with prostaglandin F2 alpha (10(-6) M), L-NMMA (2.5 x 10(-4) M) increased tension (+39.9 +/- 7.9% of PGF2 alpha-induced constriction) when endothelium was intact, but L-NMMA caused a significant reduction in tension when endothelium was removed (Emax -52.2 +/- 10.3%; P < .05). The reduction in tension after L-NMMA was greater in the absence of indomethacin (Emax -79.8 +/- 4.1%; P < .05). It has been suggested previously that biotransformation of L-NMMA to L-arginine may have contributed to vasorelaxation; L-arginine is the endogenous substrate of nitric oxide synthase. However L-arginine (10(-3) M) did not affect the fall in tension produced by L-NMMA (Emax -69.0 +/- 14.2% in the absence of indomethacin). We also found that incubation with the protein synthesis inhibitor, cycloheximide, did not block the L-NMMA- induced fall in vascular tension; in fact, it increased the magnitude of the relaxant effect (-95.4 +/- 2.5%, experiments performed without indomethacin).(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 264, Issue 1, pp. 265-270, 01/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics