Transnitrosation as a predominant mechanism in the hypotensive effect of S-nitrosoglutathione.
S-Nitrosoglutathione, a possible intermediate in the pharmacological mechanisms of many vasodilators, undergoes hemolysis at pH 7.4 and 37 degrees C to give oxidized glutathione and nitric oxide with a second-order rate constant of approximately 3 x 10(-4) M-1sec-1. At the dosages normally employed, this reaction is, therefore, too slow to be an obligatory step in the pharmacological mechanisms of those, usually, fast-acting drugs. Transfers of the nitroso moiety to another thiol or to certain hemoproteins are, however, both much faster and could be involved in those pharmacological mechanisms. Intravenously administered S-nitrosoglutathione reduced the blood pressure of anesthesized dogs and monkeys to the same extent and with essentially the same rapid onset and dissipation as sodium nitroprusside, which is the fastest-acting of those vasodilators.
Park
J W
JW
Department of Biochemistry, Kyungpook National University, Taegu, Korea.
Billman
G E
GE
Means
G E
GE
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D008401:Gas Chromatography-Mass Spectrometry; D005978:Glutathione / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008099:Liver / Q000201:enzymology; D008252:Macaca fascicularis; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D015538:Nitrosation; D009603:Nitroso Compounds / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D026422:S-Nitrosoglutathione; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
D009603:Nitroso Compounds; D013438:Sulfhydryl Compounds; D009599:Nitroprusside; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D006162:Guanylate Cyclase; D005978:Glutathione