期刊
CURRENT PHARMACEUTICAL BIOTECHNOLOGY
卷 12, 期 9, 页码 1385-1393出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138920111798280956
关键词
Oxygen-sensing; pathophysiology; pulmonary circulation; systemic circulation; vasocontriction; vasodilatation
资金
- Danish Research Council
- Villum Kann Rasmussen Foundation
- Novo Nordisk
- L'Oreal-UNESCO
- Danish Medical Research Council
Recent research has shown that the endogenous gas hydrogen sulphide (H2S) 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, H2S is synthesized from cysteine by cystathionine-gamma-lyase (CSE) in smooth muscle cells (SMC) and 3-mercaptopyruvate sulfuresterase (3MST) and CSE in the endothelial cells. In pulmonary and systemic arteries, H2S induces relaxation and/or contraction dependent on the concentration of H2S, type of vessel and species. H2S 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. H2S also relaxes SMC through the release of endothelium-derived hyperpolarizing factor (EDHF) and nitric oxide (NO) from the endothelium. H2S 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 H2S in oxygen sensing. Furthermore, reduced endogenous H2S production may also play a role in ischemic heart diseases and hypertension, and treatment with H2S donors and cysteine analogues may be beneficial in treatment of cardiovascular disease.
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