Endogenous hydrogen sulfide production confers versatile cardiovascular protection

In recent years, research has established that hydrogen sulfide (H₂S) is generated enzymatically within the body, and functions as an important modulator of physiological function—akin in this respect to the physiological gases nitric oxide (NO) and carbon monoxide (CO). Moreover, there is now substantial evidence that physiological levels of H₂S work in a wide range of complementary ways to promote and preserve cardiovascular (CV) health.1–3 Studies in rodents and in cell cultures—employing molecules which give rise to H₂S in vivo, drugs which inhibit or boost the activity of the enzymes which generate it, and transgenic rodents in which these enzymes are knocked out or upregulated—have established that physiological concentrations of H₂S can oppose atherogenesis, ameliorate systemic and pulmonary hypertension, as well as protect the heart subjected to pressure overload, endoplasmic reticulum (ER) stress or adrenergic overstimulation.1 2 4–8 With respect to atherogenesis, H₂S has been found to decrease endothelial inflammation, suppress monocyte adhesion, amplify endothelium-dependent vasodilation, decrease the formation and inflammatory activity of foam cells, inhibit smooth muscle migration, oppose intimal hyperplasia, inhibit vascular calcification and oppose thrombogenesis.1 9–21 Although H₂S does not modulate plasma lipoprotein levels, it has been shown to protect low-density lipoprotein (LDL) from oxidation mediated by the myeloperoxidase product hypochlorous acid.22 Hypochlorous acid-mediated oxidation of LDL seems likely to play a role in the pathogenesis of atherosclerosis; curiously, alpha-tocopherol, which notoriously failed to confer CV protection in multicentre trials, fails to prevent this oxidation.23–25

With respect to regulation of blood pressure (BP), H₂S acts directly as a vasodilator of smooth muscle, via activation of hyperpolarising potassium channels, and also promotes the vasodilatory activity of NO.26 27 In hearts challenged by pressure overload or adrenergic overstimulation, H_{2 …}