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The Possible Role of Hydrogen Sulfide as an Endogenous Smooth Muscle Relaxant in Synergy with Nitric Oxideā˜†

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Abstract

Hydrogen sulfide (H2S), which is well known as a toxic gas, is produced endogenously in mammalian tissues from L-cysteine mainly by two pyridoxal-5ā€²-phosphate-dependent enzymes, cystathionine Ī²-synthetase and cystathionine Ī³-lyase. Recently, we showed that cystathionine Ī²-synthetase in the brain produces H2S, and that H2S facilitates the induction of hippocampal long-term potentiation by enhancing NMDA receptor activity. Here we show that mRNA for another H2S producing enzyme, cystathionine Ī³-lyase, is expressed in the ileum, portal vein, and thoracic aorta. The ileum also expresses cystathionine Ī²-synthetase mRNA. These tissues produce H2S, and this production is blocked by cystathionine Ī²-synthetase and cystathionine Ī³-lyase specific inhibitors. Although exogenously applied H2S alone relaxed these smooth muscles, much lower concentrations of H2S greatly enhanced the smooth muscle relaxation induced by NO in the thoracic aorta. These observations suggest that the endogenous H2S may regulate smooth muscle tone in synergy with NO.

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    ā˜†

    Abbreviations: H2S, hydrogen sulfideNO, nitric oxide; CO, carbon monoxide; NaHS, sodium hydrosulfide; EDRF, endothelium-derived relaxing factor; SEM, the standard error of the mean;

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