title: Hydrogen sulfide treatment reduces blood pressure and oxidative stress in angiotensin II-induced hypertensive mice.
abstract: Hydrogen sulfide (H2S) is increasingly recognized as a gasotransmitter with protective effects in the cardiovascular system. The aim of the study was to examine the effects of chronic NaHS treatment on blood pressure, vascular function and oxidative stress in an in vivo model of hypertension and oxidative stress. Male C57Bl6/J mice were rendered hypertensive with 0.7 mg kg(-1) per day angiotensin II (AngII) for 14 days administered via implanted mini-pumps. The mice were treated with NaHS (10 μmol kg(-1) per day) to deliver H2S or an inhibitor of cystathionine-γ-lyase, DL-propargylglycine (PPG 30 mg kg(-1) per day) via intraperitoneal (i.p.) injection. Systolic blood pressure was measured and vascular function examined by myography. Vascular superoxide production was measured by lucigenin-enhanced chemiluminescence. AngII infusion significantly increased systolic blood pressure (P < 0.001). This increase was significantly attenuated by treatment with NaHS (P < 0.001). Both aortic endothelial function and NO bioavailability were significantly attenuated in the AngII group (P < 0.01) but this attenuation was reversed by NaHS treatment. Similarly, aortic superoxide anion production was significantly enhanced by AngII (P < 0.01), and this was reversed by NaHS treatment, and also exacerbated by PPG treatment (P < 0.001). These data show that in a mouse model of hypertension and oxidative stress induced by AngII, exogenous H2S treatment in vivo reduces blood pressure, endothelial dysfunction and vascular oxidative stress, while inhibiting endogenous H2S production in vivo is deleterious. This furthers the evidence that H2S is a vasoprotective molecule that may be a useful treatment target in cardiovascular disease.
authors.affiliation: Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Al-Magableh
authors.affiliation: Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Kemp-Harper
authors.affiliation: School of Medical Sciences, Health Innovations Research Institute, RMIT University, Bundoora, Victoria, Australia.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Hart
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
references.citation: Antioxid Redox Signal. 2010 May 15;12(10):1203-17
references.pmid: 19769484
references.citation: Med Gas Res. 2013 Apr 29;3(1):9
references.pmid: 23628084
references.citation: Shock. 2005 Dec;24(6):529-34
references.pmid: 16317383
references.citation: Hypertens Res. 2011 Jun;34(6):665-73
references.pmid: 21512515
references.citation: PLoS One. 2012;7(12):e53319
references.pmid: 23285278
references.citation: Trends Mol Med. 2008 Nov;14(11):495-502
references.pmid: 18929509
references.citation: EMBO J. 2001 Nov 1;20(21):6008-16
references.pmid: 11689441
references.citation: Biochemistry. 1979 Oct 16;18(21):4690-701
references.pmid: 387077
references.citation: Am J Physiol Heart Circ Physiol. 2004 Nov;287(5):H2316-23
references.pmid: 15191893
references.citation: Free Radic Res. 2009 Jun;43(6):581-93
references.pmid: 19513906
references.citation: Hypertension. 2005 Nov;46(5):1147-53
references.pmid: 16216984
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):17907-8
references.pmid: 17991773
references.citation: Hypertension. 2009 Aug;54(2):338-44
references.pmid: 19506101
references.citation: Pharmacol Ther. 2008 Dec;120(3):292-316
references.pmid: 18804122
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2014 Jan;387(1):67-74
references.pmid: 24068103
references.citation: Biochem Biophys Res Commun. 2006 Dec 15;351(2):485-91
references.pmid: 17069760
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2011 Apr;383(4):403-13
references.pmid: 21336541
references.citation: Amino Acids. 2011 Jun;41(1):113-21
references.pmid: 20191298
references.citation: Biochem Biophys Res Commun. 2004 Jan 2;313(1):22-7
references.pmid: 14672692
references.citation: Eur J Pharm Sci. 2013 Jan 23;48(1-2):211-5
references.pmid: 23148920
references.citation: Int J Impot Res. 2013 May;25(3):86-90
references.pmid: 23171981
references.citation: Free Radic Biol Med. 2011 Jan 1;50(1):196-205
references.pmid: 21034811
references.citation: Biochemistry. 2001 Jul 27;40(28):8369-77
references.pmid: 11444984
references.citation: Sci Signal. 2009 Nov 10;2(96):ra72
references.pmid: 19903941
references.citation: Chin Med J (Engl). 2011 Nov;124(22):3816-9
references.pmid: 22340247
references.citation: Clin Sci (Lond). 2012 Jul;123(2):73-91
references.pmid: 22455351
references.citation: Biochem Biophys Res Commun. 2012 May 4;421(2):164-9
references.pmid: 22503984
references.citation: Trends Pharmacol Sci. 2003 Sep;24(9):471-8
references.pmid: 12967772
references.citation: Circ Res. 2005 Apr 29;96(8):818-22
references.pmid: 15860762
references.citation: Arterioscler Thromb Vasc Biol. 2010 Oct;30(10):1998-2004
references.pmid: 20634473
references.citation: Hypertension. 2008 Apr;51(4):872-7
references.pmid: 18299484
references.citation: Eur J Pharmacol. 2013 Jan 5;698(1-3):463-9
references.pmid: 23183109
references.citation: Br J Pharmacol. 2008 Dec;155(7):984-94
references.pmid: 18846041
references.citation: PLoS One. 2011;6(6):e20813
references.pmid: 21673968
references.citation: Antioxid Redox Signal. 2009 Feb;11(2):205-14
references.pmid: 18754702
references.citation: Br J Pharmacol. 1998 Jun;124(4):719-28
references.pmid: 9690864
references.citation: FASEB J. 2004 Jul;18(10):1165-7
references.pmid: 15155563
references.citation: Br J Pharmacol. 2013 Jun;169(4):922-32
references.pmid: 23488457
references.citation: J Vasc Res. 2008;45(6):521-8
references.pmid: 18463417
references.citation: Int J Vasc Med. 2013;2013:915983
references.pmid: 23864951
references.citation: Am J Physiol Heart Circ Physiol. 2002 Aug;283(2):H474-80
references.pmid: 12124191
references.citation: Biochem J. 1982 Aug 15;206(2):267-77
references.pmid: 7150244
references.citation: J Pharmacol Exp Ther. 2008 Feb;324(2):876-82
references.pmid: 18029544
references.citation: J Neurochem. 2004 Aug;90(3):765-8
references.pmid: 15255956
references.citation: Front Biosci (Elite Ed). 2011 Jan 01;3:736-49
references.pmid: 21196347
references.citation: J Cardiovasc Pharmacol. 2011 Dec;58(6):560-9
references.pmid: 21283022
references.citation: Hypertens Res. 2008 Aug;31(8):1619-30
references.pmid: 18971538
references.citation: Biochem Biophys Res Commun. 2005 Jan 28;326(4):794-8
references.pmid: 15607739
references.citation: Nature. 1986 Apr 3-9;320(6061):454-6
references.pmid: 3007998
references.citation: Hypertens Res. 2011 Apr;34(4):431-40
references.pmid: 21228777
references.citation: Biochem J. 2012 Jan 15;441(2):609-21
references.pmid: 21950347
references.citation: Nat Rev Drug Discov. 2011 Jun;10(6):453-71
references.pmid: 21629295
references.citation: J Cell Mol Med. 2013 Jul;17(7):879-88
references.pmid: 23742697
references.citation: FASEB J. 2002 Nov;16(13):1792-8
references.pmid: 12409322
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1994 May;349(5):538-42
references.pmid: 8065468
references.citation: Physiol Rev. 2007 Jan;87(1):315-424
references.pmid: 17237348
references.citation: Science. 2008 Oct 24;322(5901):587-90
references.pmid: 18948540
references.citation: Biochem Pharmacol. 1982 May 15;31(10):1903-6
references.pmid: 6285929
references.citation: Free Radic Biol Med. 2008 Dec 15;45(12):1705-13
references.pmid: 18848879
references.citation: J Am Soc Nephrol. 2005 Aug;16(8):2346-53
references.pmid: 15944340
references.citation: Circulation. 2008 May 6;117(18):2351-60
references.pmid: 18443240
references.citation: Free Radic Res. 2003 Feb;37(2):121-7
references.pmid: 12653200
references.citation: Physiol Rep. 2013 Oct;1(5):e00111
references.pmid: 24303182
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2012 Oct;385(10):991-1002
references.pmid: 22801977
references.citation: Antioxid Redox Signal. 2010 Jan;12(1):1-13
references.pmid: 19852698
references.citation: J Biochem. 2009 Nov;146(5):623-6
references.pmid: 19605461
references.citation: Antioxid Redox Signal. 2012 Jul 1;17(1):119-40
references.pmid: 22432697