The Role of Endogenous H2S in Cardiovascular Physiology

摘要

Recent research has shown that the endogenous gas hydrogen sulphide (H_2S) is a signalling molecule of considerable biological potential and has been suggested to be involved in a vast number of physiological processes. In the vascular system, HjS is synthesized from cysteine by cystathionine-y-lyase (CSE) in smooth muscle cells (SMC) and 3-mercaptopyruvate sulfuresterase (3MST) and CSE in the endothelial cells. In pulmonary and systemic arteries, H_2S induces relaxation and/or contraction dependent on the concentration of H_2S, type of vessel and species. H_2S relaxes SMC through a direct effect on KATP-channels or Kv-channels causing hyperpolarization and closure of voltage-dependent Ca2+-channels followed by a reduction in intracellular calcium. H_2S also relaxes SMC through the release of endothe-lium-derived hyperpolarizing factor (EDHF) and nitric oxide (NO) from the endothelium. H_2S contracts SMC through a reduction in nitric oxide (NO) availability by reacting with NO forming a nitrosothiol compound and through an inhibitory effect on endothelial nitric oxide synthase (eNOS) as well as a reduction in SMC cyclic AMP concentration. Evidence supports a role for H_2S in oxygen sensing. Furthermore, reduced endogenous H_2S production may also play a role in ischemic heart diseases and hypertension, and treatment with H_2S donors and cysteine analogues may be beneficial in treatment of cardiovascular disease.