Effect of substituted arginine compounds on superoxide production in the rabbit aorta.
Superoxide anion (O2-) blocks the vascular effect of endothelium-derived relaxing factor (EDRF). Previous reports implicate L-arginine or N alpha-substituted arginine compounds as precursors of EDRF. Employing a microassay for the measurement of O2- production by rabbit aortic rings, which is based on the established method of reduction of cytochrome c by O2-, we studied the interaction between O2- and EDRF using L-arginine, an N-substituted arginine compound, namely, N alpha-benzoyl-L-arginine ethyl ester (BAEE), sodium nitroprusside and NG-monomethyl-L-arginine (NMMA), a putative specific inhibitor of EDRF synthesis. Measurements of O2- production were made under basal conditions and upon stimulation with alloxan, the diabetogenic, O(2-)-generating compound. Both BAEE, an EDRF-generating agent (0.3 and 3.0 mM) and sodium nitroprusside, an NO-generating compound (1.7 and 3.4 microM), significantly reduced alloxan-stimulated O2- production, but L-arginine (0.6-3.0 mM) paradoxically increased O2- generation. NMMA (1.0 mM) blocked the inhibitory effect of BAEE on O2- production in an endothelium-dependent manner. Because NMMA is an inhibitor of EDRF, these results suggest that BAEE, but not L-arginine, reduces O2- produced by the endothelium of the rabbit aorta through a mechanism involving EDRF generation.
Heim
K F
KF
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC.
Thomas
G
G
Ramwell
P W
PW
D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D013481:Superoxides / Q000378:metabolism*; D019323:omega-N-Methylarginine
D013481:Superoxides; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000496:Alloxan; D001120:Arginine; C012208:benzoyl L-arginine methyl ester