Chronic sodium hydrosulfide treatment decreases medial thickening of intramyocardial coronary arterioles, interstitial fibrosis, and ROS production in spontaneously hypertensive rats

1 Department of Physiology and Pathophysiology, 2 School of Pharmacy, and 3 The Children's Hospital, Fudan University Shanghai Medical College, Shanghai, China; Cardiovascular Biology Research Group, Departments of 4 Pharmacology and 5 Biochemistry, National University of Singapore, Singapore Submitted 21 January 2007 ; accepted in final form 2 July 2007 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 µmol·kg –1 ·day –1 ), a combination of NaHS (30 µmol·kg –1 ·day –1 ) and glibenclamide (5 mg·kg –1 ·day –1 ), glibenclamide alone (5 mg·kg –1 ·day –1 ), hydralazine alone (10 mg·kg –1 ·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 µm, 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. left-ventricular remodeling; gasotransmitter; hypertension; hydrogen sulfide Address for reprint requests and other correspondence: Y.-C. Zhu, Dept. of Physiology and Pathophysiology, Fudan Univ. Shanghai Medical College, 138 Yi Xue Yuan Road, Shanghai 200032, China (e-mail: yczhu{at}shmu.edu.cn )