Emerging role of hydrogen sulfide in hypertension and related cardiovascular diseases

Abstract

Hydrogen sulfide (H2S) has traditionally been viewed as a highly toxic gas; however, recent studies have implicated H2S as a third member of the gasotransmitter family, exhibiting properties similar to NO and carbon monoxide. Accumulating evidence has suggested that H2S influences a wide range of physiological and pathological processes, among which blood vessel relaxation, cardioprotection and atherosclerosis have been particularly studied. In the cardiovascular system, H2S production is predominantly catalyzed by cystathionine γ-lyase (CSE). Decreased endogenous H2S levels have been found in hypertensive patients and animals, and CSE −/− mice develop hypertension with age, suggesting that a deficiency in H2S contributes importantly to BP regulation. H2S supplementation attenuates hypertension in different hypertensive animal models. The mechanism by which H2S was originally proposed to attenuate hypertension was by virtue of its action on vascular tone, which may be related to effects on different ion channels. Both H2S and NO cause vasodilatation and there is cross-talk between these two molecules to regulate BP. Suppression of oxidative stress may also contribute to antihypertensive effects of H2S. This review also summarizes the state of research on H2S and hypertension in China. A better understanding of the role of H2S in hypertension and related cardiovascular diseases will allow novel strategies to be devised for their treatment. LINKED ARTICLESThis article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10. 1111/bph.2015.172.issue-23 Abbreviation 2K1C, two-kidney-one-clip; Ang II; angiotensin II; AOA, aminooxyacetic acid; AT1 receptor, angiotensin II type 1 receptor; CBS, cystathionine-β-synthase; CO, carbon monoxide; CSE, cystathionine-γ-lyase; DBP, diastolic BP; eNOS, endothelial NOS; H2S, hydrogen sulfide; I/R, ischaemia/reperfusion; L-NAME, N G -nitro-l-arginine methyl ester; MAP, mean arterial pressure; MPST, 3-mercaptopyruvate sulfurtransferase; MWT, medial wall thickness; PAAT, pulmonary arterial acceleration time; PAG; DL-propargylglycine; PHT, pulmonary hypertension; RVET, right ventricular ejection time; RVH, right ventricular hypertrophy; SBP, systolic BP; SHR, spontaneously hypertensive rat; SMCs, smooth muscle cells; VEGFR-1, soluble fms-like tyrosine kinase 1; VD, vas deferens IntroductionIn recent years, the 'gasotransmitters' NO, carbon monoxide (CO) and hydrogen sulfide (H2S) have been the object of intense research (Papapetropoulos et al., 2014). In the last two decades, NO has been extensively studied; and in more recent times, the importance of H2S in cardiovascular regulation has become increasingly apparent (Polhemus and Lefer, 2014). Until the H2S content within the brain was first measured in postmortem studies in 1989, H2S was traditionally viewed as a highly toxic gas devoid of beneficial biological or physiological functions (Goodwin et al., 1989). Subsequently, H2S quic...

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