Vasomotor responses of canine coronary arterial rings to NG-monomethyl-L-arginine and N omega nitro L-arginine methyl ester.
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)
Winn
M J
MJ
Department of Pharmacology, University of Alabama, Birmingham.
Asante
N K
NK
Ku
D D
DD
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D001711:Biotransformation; D003331:Coronary Vessels / Q000294:innervation*; D003513:Cycloheximide / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D014666:Vasomotor System / Q000187:drug effects*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D003513:Cycloheximide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin