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.