Biological activation of N(G)-nitro-D-arginine by kidney homogenate .
N(G)-nitro-L-arginine (L-NNA) and D-NNA have been shown to inhibit endothelium-dependent relaxation. This study examined if the inhibitory effect of L-NNA or D-NNA on relaxation is increased following incubation of the drug with the supernatant of tissue homogenates. Acetylcholine (ACh) caused concentration-dependent relaxation of pre-constricted rat aortic rings with maximum relaxation of 95%. Maximum relaxations to ACh were reduced to 71 and 37% in the presence of D-NNA (40 microM) and L-NNA (1 microM), respectively. Relaxation to ACh was further reduced to 18% in the presence of D-NNA that was incubated for 1 h with the supernatant of kidney homogenate, but unaffected by D-NNA incubated with the supernatant of trichloroacetic acid-denatured kidney homogenate. Incubation of L-NNA (1 microM) with either kidney supernatant or denatured kidney supernatant for 1 h did not affect its inhibitory effect on ACh-induced relaxation. Neither 1 h's incubation with plasma, or supernatants of liver, lungs or aorta homogenates affected the inhibitory action of D-NNA (40 or 120 microM) on ACh-induced relaxation. After D-NNA was incubated in kidney supernatant, its inhibitory effect on ACh-induced relaxation of the aorta was abolished by pretreatment of the aorta with L-arginine (L-Arg) but not D-Arg suggesting involvement of the L-Arg pathway. The results suggest that D-NNA is converted by the kidney to a compound that acts similar to L-NNA. There appears to be little conversion of L-NNA to D-NNA.
Cheng
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Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
Wang
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YX
Pang
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism / Q000502:physiology*; D008099:Liver / Q000502:physiology; D008168:Lung / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019335:Nitroarginine / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D019335:Nitroarginine; D001120:Arginine; D000109:Acetylcholine