Is guanidino succinate a precursor for nitric oxide synthesis in rat vascular tissue?
Although L-Arginine (L-Arg) is considered the physiological precursor of nitric oxide (NO) synthesis in endothelial cells, recent experiments suggested that another guanidino derivative, guanidino succinate, may also serve as a major source of NO in this tissue. We tested this hypothesis in rat aortas, using two experimental situations in which L-Arg had previously shown significant activity, i.e., the ability to counteract contractile responses to the L-Arg analogue NG-nitro-L-arginine methyl ester (L-NAME) and the relaxation observed after prolonged incubation in physiologic buffer. Rat aortic rings, with or without endothelium, were suspended in organ chambers for recording of isometric tension and were contracted by phenylephrine (PE). After a brief incubation period (0.5 h), L-Arg, D-Arg, or guanidino succinate induced only minor relaxations in rings with or without endothelium. In the presence of L-NAME, L-Arg (but not the D-enantiomer), induced concentration-dependent relaxations of rings with endothelium (relaxation to L-Arg 10(-3) M 52 +/- 13%), reflecting a reversal by L-Arg of the L-NAME-induced potentiation of the contraction to PE. In contrast to L-Arg, guanidino succinate was less effective in the presence than in the absence of L-NAME (relaxation to guanidino succinate 10(-3) M before L-NAME 37 +/- 8% and after L-NAME 14 +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)
Richard
V
V
Department of Pharmacology, VACOMED, IFRMP, Rouen University School of Medicine, France.
Henry
J P
JP
Thuillez
C
C
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D006146:Guanidines / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013386:Succinates / Q000378:metabolism* / Q000494:pharmacology
D006146:Guanidines; D013386:Succinates; D010656:Phenylephrine; D009569:Nitric Oxide; C001318:guanidinosuccinic acid; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester