NG-hydroxy-L-arginine and hydroxyguanidine potentiate the biological activity of endothelium-derived relaxing factor released from the rabbit aorta.
We investigated the effects of NG-hydroxy-L-arginine (L-HOArg) and hydroxyguanidine (HOG) on the synthesis and vasorelaxant activity of endothelium-derived relaxing factor (NO) released from the rabbit aortic endothelium. Both L-HOArg (10 microM) and HOG (10 microM) equally potentiated the vasorelaxant activity of NO released by Ach (0.1 or 0.3 microM) from the luminally perfused rabbit aorta and bioassayed using the superfused strips of the endothelium-denuded rabbit aorta. This potentiation was caused by the generation of a more stable vasodilator during the chemical reaction of L-HOArg or HOG with NO and it was abolished by NG-nitro-L-arginine methyl ester (L-NO2Arg, 10 microM). In contrast, in organ baths, L-HOArg (10 microM) or HOG (10 microM) did not affect the relaxations of intact rabbit aortic rings induced by Ach (0.01-1 microM). At concentrations higher than 10 microM, both L-HOArg and HOG were endothelium-independent vasorelaxants. However, L-HOArg (100 microM) prevented the inhibition by L-NO2Arg (10 microM) of Ach-induced relaxations of bathed aortic rings which indicates that L-HOArg is still a substrate for the NO synthase in the endothelium of the rabbit aorta.
Zembowicz
A
A
Department of Pharmacology, Copernicus Academy of Medicine, Kraków, Poland.
Chłopicki
S
S
Radziszewski
W
W
Vane
J R
JR
Gryglewski
R J
RJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000502:physiology*; D006146:Guanidines / Q000494:pharmacology*; D006898:Hydroxylamines; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D010477:Perfusion; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
D000963:Antimetabolites; D006146:Guanidines; D006898:Hydroxylamines; D009569:Nitric Oxide; C007985:N(5)-hydroxy-L-arginine; C029604:hydroxyguanidine; D001120:Arginine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester