Emerging role of hydrogen sulfide in hypertension and related cardiovascular diseases

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.

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This 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

Tables of Links

TARGETS
GPCRa	Catalytic receptorsd
AT1 receptor	VEGFR‐1
Muscarinic receptors	Enzymese
Thromboxane A2 receptor	CBS
Ligand‐gated ion channelsb	CSE
Epithelial sodium channels (ENaC)	eNOS
Ion channelsc	ERK1/2
BKCa channels	HO1
CaV channels	p38MAPK
CaV1.1‐1.4 (L‐type Ca) channels	PKG
KATP channels	PTEN
Kir channels	MPST
KV channels
KV7.x (KCNQ) channels

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LIGANDS
ACh	L‐NAME
Angiotensin II	NaHS
AOA	Nifedipine
Carbachol	Nitric oxide (NO)
Glibenclamide	Noradrenaline
Homocysteine	Phenylephrine
Iberiotoxin	Tetraethylammonium
L‐arginine	U46619
L‐cysteine	XE991

Open in a separate windowThese Tables list key protein targets and ligands in this article which are hyperlinked to corresponding entries in http://www.guidetopharmacology.org, the common portal for data from the IUPHAR/BPS Guide to PHARMACOLOGY (Pawson et al., 2014) and are permanently archived in the Concise Guide to PHARMACOLOGY 2013/14 (^a,b,c,d,eAlexander et al., 2013a, 2013b, 2013c, 2013d, 2013e).