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

Abstract

. 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...

Hydrogen Sulfide Inhibits High Glucose-induced Matrix Protein Synthesis by Activating AMP-activated Protein Kinase in Renal Epithelial Cells

“…Both hypertrophy and renal fibrosis require stimulation of protein synthesis. Previous studies showed that hydrogen sulfide reduced hypertrophy of intramyocardial arterioles and cardiac ventricular fibrosis (9), supporting the contention that it is an inhibitor of protein synthesis. There is consensus that the initiation phase of mRNA translation is a rate-limiting step in synthesis of proteins (22).…”

Hydrogen Sulfide Regulates Na+/H+ Exchanger Activity via Stimulation of Phosphoinositide 3-Kinase/Akt and Protein Kinase G Pathways

“…This is because, apart from inhibition of NHE-1, H 2 S also protects the heart via suppression of ␤-adrenoceptor function and stimulation of various protein kinases and cardioprotective mediators such as prostaglandin E 2 and NO Hu et al, 2008;Pan et al, 2008Pan et al, , 2009Yong et al, 2008b). In addition, H 2 S has been found to be useful in treating renin-dependent hypertension (Lu et al, 2010b), chronic heart failure (Calvert et al, 2010), and hypertrophy (Shi et al, 2007). These data suggest that H 2 S treatment may provide multiple cardioprotective effects.…”

H2S does not regulate proliferation via T-type Ca2+ channels

“…In addition to its tonic, physiological role as a regulator of blood pressure [34], it is also a major modifier of tissue remodelling resulting from cardiovascular diseases. Thus, for example, cardiac arteriolar hypertrophy and interstitial fibrosis observed in spontaneously hypertensive rats was prevented by daily administration of the H2S donor NaHS [35]. Furthermore, neointima formation and VSMC proliferation following carotid artery balloon injury was suppressed following chronic NaHS administration [36].…”