title: Chronic sodium hydrosulfide treatment decreases medial thickening of intramyocardial coronary arterioles, interstitial fibrosis, and ROS production in spontaneously hypertensive rats.
abstract: Hydrogen sulfide (H(2)S) is a gasotransmitter that regulates cardiovascular functions. The present study aimed to examine the hypothesis that chronic treatment with sodium hydrosulfide (NaHS, an H(2)S donor) is able to prevent left-ventricular remodeling in spontaneously hypertensive rats (SHR). Four-week-old SHR were treated with NaHS (10, 30, and 90 micromol x kg(-1) x day(-1)), a combination of NaHS (30 micromol x kg(-1) x day(-1)) and glibenclamide (5 mg x kg(-1) x day(-1)), glibenclamide alone (5 mg x kg(-1) x day(-1)), hydralazine alone (10 mg x kg(-1) x day(-1)), and placebo for 3 mo. At the end of the treatment period, variables such as cardiac geometry and function, intramyocardial arterioles ranging in diameter from 25 to 100 microm, perivascular and interstitial collagen content, reactive oxygen species (ROS), thiol groups, conjugated dienes, and DNA base modification were examined. The novel finding of the present study is that chronic NaHS treatment prevented the hypertrophy of intramyocardial arterioles and ventricular fibrosis, as well as decreased myocardial ROS and conjugated diene levels. The cardioprotective effects were blunted by coadministration of glibenclamide, suggesting a role of ATP-sensitive potassium channels in mediating the action of NaHS. Hydralazine caused a comparable reduction of blood pressure compared with NaHS treatment; however, it exerted no effect on the remodeling process or on ROS and conjugated diene levels. Moreover, NaHS treatment caused an increase in myocardial thiol group levels, whereas DNA base modification was not altered by NaHS treatment. In conclusion, the superior cardioprotective effects of NaHS treatment are worthy to be further explored to develop novel therapeutic approaches for the treatment of cardiac remodeling in hypertension.
authors.affiliation: Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Ying-Xian
authors.initials: YX
authors.lastname: Shi
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Yi-Zhun
authors.initials: YZ
authors.lastname: Zhu
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Huang
authors.forename: Philip Keith
authors.initials: PK
authors.lastname: Moore
authors.forename: Shan-Hong
authors.initials: SH
authors.lastname: Huang
authors.forename: Tai
authors.initials: T
authors.lastname: Yao
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001774:Blood Chemical Analysis; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005355:Fibrosis; D005905:Glyburide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology* / Q000627:therapeutic use; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D013440:Sulfides; D006830:Hydralazine; D003094:Collagen; D004247:DNA; C025451:sodium bisulfide; D005905:Glyburide