cardiovascular-agents and sodium-sulfide

Hydrogen sulfide (H(2)S) is a gasomediator synthesized from L- and D-cysteine in various tissues. It is involved in a number of physiological and pathological processes. H(2)S exhibits antiatherosclerotic, vasodilator, and proangiogenic properties, and protects the kidney and heart from damage following ischemia/reperfusion injury. H(2)S donors may be natural or synthetic, and may be used for the safe treatment of a wide range of diseases. This review article summarizes the current state of knowledge of the therapeutic function of H(2)S.

Topics: Angiogenesis Inducing Agents; Cardiovascular Agents; Cysteine; Diclofenac; Disulfides; Heart; Humans; Hydrogen Sulfide; Kidney; Levodopa; Prostaglandins F, Synthetic; Reperfusion Injury; Sulfides; Thioctic Acid; Thiones; Vasodilator Agents

Therapeutic strategies aimed at increasing hydrogen sulfide (H2S) levels exert cytoprotective effects in various models of cardiovascular injury. However, the underlying mechanism(s) responsible for this protection remain to be fully elucidated. Nuclear factor E2-related factor 2 (Nrf2) is a cellular target of H2S and facilitator of H2S-mediated cardioprotection after acute myocardial infarction. Here, we tested the hypothesis that Nrf2 mediates the cardioprotective effects of H2S therapy in the setting of heart failure.. Mice (12 weeks of age) deficient in Nrf2 (Nrf2 KO; C57BL/6J background) and wild-type littermates were subjected to ischemic-induced heart failure. Wild-type mice treated with H2S in the form of sodium sulfide (Na2S) displayed enhanced Nrf2 signaling, improved left ventricular function, and less cardiac hypertrophy after the induction of heart failure. In contrast, Na2S therapy failed to provide protection against heart failure in Nrf2 KO mice. Studies aimed at evaluating the underlying cardioprotective mechanisms found that Na2S increased the expression of proteasome subunits, resulting in an increased proteasome activity and a reduction in the accumulation of damaged proteins. In contrast, Na2S therapy failed to enhance the proteasome and failed to attenuate the accumulation of damaged proteins in Nrf2 KO mice. Additionally, Na2S failed to improve cardiac function when the proteasome was inhibited.. These findings indicate that Na2S therapy enhances proteasomal activity and function during the development of heart failure in an Nrf2-dependent manner and that this enhancement leads to attenuation in cardiac dysfunction.

Topics: Animals; Cardiovascular Agents; Disease Models, Animal; Endoplasmic Reticulum Stress; Heart Failure; Hydrogen Sulfide; Hypertrophy, Left Ventricular; Male; Mice, Inbred C57BL; Mice, Knockout; Myocardial Ischemia; Myocardium; NF-E2-Related Factor 2; Oxidative Stress; Proteasome Endopeptidase Complex; Signal Transduction; Sulfides; Time Factors; Ventricular Function, Left