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Cardiovascular (CV) research has largely been focused on two endogenously produced gaseous signaling molecules, namely, nitric oxide (NO) and carbon monoxide (CO). These gaseous messengers are both highly conserved evolutionarily and synthesized by endogenous enzyme systems. Extensive research efforts have uniformly demonstrated that CO- and NO-based therapeutics protect the brain, heart, and circulation against a number of CV disease states (1–3). However, controversy exists regarding the therapeutic value of both CO and NO, with some studies citing NO cytotoxicity at very high levels and under certain conditions (2). The toxic effects of NO are related to the highly reactive nature of NO and its interaction with superoxide to form the potent oxidant peroxynitrite (ONOO−) (2). Very recently, a third endogenously produced gaseous signaling molecule, hydrogen sulfide (H2S), has emerged as a potentially important mediator of CV homeo stasis and cytoprotection (3). In this issue of PNAS, Benavides et al. (4) reveal that the vasculoprotective and antihypertensive effects of dietary garlic (Allium sativum) are mediated in large part via the generation of H2S. Previous studies indicate that dietary garlic consumption is inversely correlated with the progression and severity of CV disease and that it affects a lower incidence of hypertension (5). However, the mechanism(s) by which consumption of garlic attenuates CV disease has in large part remained a mystery. Benavides et al. (4) elegantly demonstrate that garlic-derived organic polysulfides are converted by red blood cells (RBCs) into hydrogen sulfide gas. Interestingly, the garlic bulbs used for this study were obtained from local supermarkets in the city of Birmingham, AL, and then pressed by the investigators to obtain garlic juice on the day of the experiment. The bioconversion of polysulfides to H2S is enhanced by glucose-maintained cytosolic glutathione levels and depends on reduced …

A new gaseous signaling molecule emerges: Cardioprotective role of hydrogen sulfide