Effects of guanidino and uremic compounds on nitric oxide pathways.

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MacAllister RJ, Whitley GS, Vallance P

Effects of guanidino and uremic compounds on nitric oxide pathways.

Kidney Int. 1994 Mar;45(3):737-42. doi: 10.1038/ki.1994.98.

PubMed ID

7515129 [ View in PubMed

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Abstract

Aminoguanidine, NG-monomethyl-L-arginine (L-NMMA), NGNGdimethyl-L-arginine (asymmetric dimethylarginine; ADMA), creatinine, guanidinosuccinic acid, guanidinoproprionic acid and methylguanidine were added to cultures of activated murine macrophages. Only aminoguanidine, ADMA, L-NMMA and methylguanidine inhibited nitrite production in a dose-dependent manner. In the presence of 100 microM arginine, nitrite production was inhibited by 31.8 +/- 7.1% by ADMA (100 microM; P < 0.01) but the same dose of methylguanidine was without effect. A higher dose of methylguanidine (1000 microM) inhibited nitrite production by 47.6 +/- 5.6% (P < 0.001). The effects of these compounds were also tested on relaxation of human saphenous veins. L-NMMA and ADMA inhibited endothelium-dependent relaxations (EC50 = 4.7 +/- 1.1 microM and 17.9 +/- 4.9 microM, respectively); methylguanidine caused endothelium-independent contractions and reversed the relaxations to bradykinin and sodium nitroprusside (EC50 > 100 microM); aminoguanidine was without effect. The results of this study suggest that of the guanidino compounds which accumulate in renal failure, only ADMA is a potent inhibitor of nitric oxide (NO) synthesis. Methylguanidine is a weak inhibitor of nitric oxide synthesis, whereas the closely related compound aminoguanidine appears to inhibit selectively the inducible isoform of nitric oxide synthase and has no effect on constitutive NO synthase in human veins.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pimagedine	Nitric oxide synthase, inducible	Protein	Humans	Yes	Inhibitor Downregulator	Details