The role of endogenous H2S in cardiovascular physiology.
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-γ-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.
Department of Pharmacology, Aarhus University, Wilhelm Meyers Alle 4, Building 1240, DK-8000 Aarhus C, Denmark. nini.jensen@biology.au.dk
Nini
N
Skovgaard
Anja
A
Gouliaev
Mathilde
M
Aalling
Ulf
U
Simonsen
D000818:Animals; D002318:Cardiovascular Diseases / Q000503:physiopathology; D002320:Cardiovascular Physiological Phenomena; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000502:physiology
D006862:Hydrogen Sulfide