. Chronic sodium hydrosulfide treatment decreases medial thickening of intramyocardial coronary arterioles, interstitial fibrosis, and ROS production in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 293: H2093-H2100, 2007. First published July 13, 2007; doi:10.1152/ajpheart.00088.2007.-Hydrogen sulfide (H2S) is a gasotransmitter that regulates cardiovascular functions. The present study aimed to examine the hypothesis that chronic treatment with sodium hydrosulfide (NaHS, an H2S 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 ), 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 m, 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 HYPERTENSION-INDUCED left-ventricular hypertrophy is recognized as an independent risk factor for myocardial ischemia, dysfunction, infarction, and heart failure (26). Structural remodeling of coronary arterioles and extracellular matrix becomes obvious in hypertrophied left ventricle (LV) in 4-mo-old spontaneously hypertensive rats (SHR) (15). Hypertension-induced medial thickening of intramyocardial coronary arterioles results in stenosis of the coronary arterioles and consequent myocardial ischemia and dysfunction (19), whereas perivascular fibrosis may induce a compression on the coronary arterioles and therefore account for a reduction in coronary vasodilator reserve. Moreover, an accumulation of fibrillar collagen in the interstitial space of hypertrophied myocardium has been held responsible for abnormal ventricular wall stiffness and for impaired cardiac pumping capacity (12,20). In this context, the aim of antihypertensive therapy is not only to decrease blood pressure (BP) but also to reduce hypertrophy of intramyocardial coronary arterioles and left-ventricular inte...
