Abstract

Recent studies suggest that apart from nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfi de (H2S) is another inorganic gaseous mediator in the cardiovascular system. H2S is synthesized from L-cysteine by either cystathionine b-synthase (CBS) or cystathionine g-lyase (CSE), both using pyridoxal 5’-phosphate (vitamin B6) as a cofactor. CBS is the main H2S-producing enzyme in the brain and CSE is involved in H2S formation in the cardiovascular system. H2S induces hypotension in vivo and vasodilation in vitro by opening KATP channels in vascular smooth muscle cells. Chronic administration of CSE inhibitor induces arterial hypertension in the rat. In addition, decreased H2S generation has been demonstrated in the vasculature of spontaneously hypertensive rat, in experimental hypertension induced by NO synthase blockade, and in hypoxia-induced pulmonary hypertension, and administration of exogenous H2S donor has signifi cant therapeutic effects in these models. Defi ciency of H2S may contribute to atherogenesis in some patients with hyperhomocysteinemia, in whom the metabolism of homocysteine to cysteine and H2S is compromised by vitamin B6 defi ciency. Reduced H2S production in the brain was observed in patients with Alzheimer’s disease. On the other hand, excess of H2S may lead to mental homoretardation in patients with Down’s syndrome and may be involved in the pathogenesis of hypotension associated with septic shock.

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