Hydrogen sulfide mediates the vasoactivity of garlic

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 46; pp. 17977 - 17982
• Main Authors: Benavides, Gloria A, Squadrito, Giuseppe L, Mills, Robert W, Patel, Hetal D, Isbell, T. Scott, Patel, Rakesh P, Darley-Usmar, Victor M, Doeller, Jeannette E, Kraus, David W
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 13.11.2007; National Acad Sciences
• Series: From the Cover
• Subjects: Acetylcysteine - pharmacology; Aorta; Assembly lines; Biological Sciences; cardioprotective effect; Cardiovascular disease; Cardiovascular diseases; cardiovascular system; Chromatography, High Pressure Liquid; Coronary vessels; Disulfides; Electrochemistry; Erythrocytes; Erythrocytes - drug effects; Erythrocytes - metabolism; food intake; Garlic; Garlic - chemistry; Glutathione - blood; Glutathione Disulfide - blood; Humans; Hydrogen; Hydrogen sulfide; Hydrogen Sulfide - blood; Hydrogen Sulfide - pharmacology; metabolism; organic polysulfides; organic sulfur compounds; Polysulfides; Respirometers; Risk factors; Sensors; Sulfides; Sulfur; Thiols; Vasodilation
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0705710104

The consumption of garlic is inversely correlated with the progression of cardiovascular disease, although the responsible mechanisms remain unclear. Here we show that human RBCs convert garlic-derived organic polysulfides into hydrogen sulfide (H₂S), an endogenous cardioprotective vascular cell signaling molecule. This H₂S production, measured in real time by a novel polarographic H₂S sensor, is supported by glucose-maintained cytosolic glutathione levels and is to a large extent reliant on reduced thiols in or on the RBC membrane. H₂S production from organic polysulfides is facilitated by allyl substituents and by increasing numbers of tethering sulfur atoms. Allyl-substituted polysulfides undergo nucleophilic substitution at the α carbon of the allyl substituent, thereby forming a hydropolysulfide (RSnH), a key intermediate during the formation of H₂S. Organic polysulfides (R-Sn-R'; n > 2) also undergo nucleophilic substitution at a sulfur atom, yielding RSnH and H₂S. Intact aorta rings, under physiologically relevant oxygen levels, also metabolize garlic-derived organic polysulfides to liberate H₂S. The vasoactivity of garlic compounds is synchronous with H₂S production, and their potency to mediate relaxation increases with H₂S yield, strongly supporting our hypothesis that H₂S mediates the vasoactivity of garlic. Our results also suggest that the capacity to produce H₂S can be used to standardize garlic dietary supplements.