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Hydrogen sulfide: from the smell of the past to the mediator of the future?

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Abstract

Gases such as nitric oxide and carbon monoxide play important roles both in normal physiology and in disease. In recent years, interest has been directed towards other naturally occurring gases, notably hydrogen sulfide (H2S), which is both a potent vasodilator and a mediator of long-term potentiation in the brain. This article focuses on recent work that suggests a role for H2S, and perhaps other gases, in the CNS and cardiovascular system.

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Hydrogen sulfide formation in the CNS – new insights and control mechanisms

Several recent publications have probed the mechanism(s) by which H2S formation by brain CBS can be controlled. Such work can provide important clues to the potential biological roles of this gas in the CNS. It is now clear that brain CBS [like nitric oxide synthase (NOS)] activity is both Ca2+ and calmodulin dependent [3], suggesting that ‘short-term’ control of neuronal H2S production by this enzyme might be achieved by the influx of Ca2+ following depolarization. The existence of such a

Does hydrogen sulfide contribute to CNS disease?

The presence of CBS, coupled with the identification of physiologically relevant amounts of H2S, in the brains of several species including humans suggested a role for this gas in CNS function [2]. Mechanistic studies have revealed that H2S increases cAMP levels in neuronal and glial cell lines and primary neuron cultures and also hyperpolarizes CA1 and dorsal raphe neurons most probably by activating K+ATP channels. In addition, H2S interferes with glutamate-mediated neurotransmission by an

Hydrogen sulfide and the cardiovascular system

H2S relaxes vascular smooth muscle both in vitro and in vivo most probably by opening vascular smooth muscle K+ATP channels. This is a general effect of H2S on smooth muscle because reduced spontaneous contractility of the rabbit ileum and inhibition of electrically evoked contractions of the guinea-pig ileum and rat vas deferens is a feature of this molecule [11].

Whether H2S plays a part in the control of blood pressure or vascular perfusion in health or disease has yet to be properly

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