Hydrogen sulfide generation protects against renal ischemia/reperfusion-induced cardiac hypertrophy and arrhythmia via amelioration of connexin- 43 expression and opening of KATP channels

Abstract

Hydrogen sulfide has been recently studied as a potential treatment for many cardiovascular disorders. Here, we describe its role in I/R-induced cardiac hypertrophy and arrhythmia model. Thirty six male Sprague Dawley rats were used in this study. Rats were randomly divided into 6 groups, G 1(n = 6/group): control negative: received saline, G2, I/R rats, (I/R, n = 6), after right nephrectomy, the rats were subjected to left kidney ischemia for 45 minutes followed by reperfusion:,G3, I/R rats in which rats were treated by NaHS, the donor of H 2 S (5 mg/kg/day×14 days) intraperitoneal,G4, I/R rats in which rats were treated by the blocker of H 2 S aminooxyacetic acid (10 mg/kg/day×14 days) intraperitoneal,G5, I/R rats in which rats were treated by converting enzyme inhibitor (Captopril) (50 mg/Kg/day ×14 days) and, G6, I/R rats in which rats were treated by NaHS and K ATP channel blocker (Glibenclamide) (20 mg/kg/day ×14 days). NaHS led to a highly significant decrease in the duration of ventricular action potential indicated by QTc. Furthermore, it decreased, significantly, both of mean blood pressure and plasma renin activity. Moreover, H 2 S donor and converting enzyme inhibition increased the expression of CX-43. While (I/R + NaHS + K ATP channel block) led to a non-significant decreased in the duration of QTc interval. This showed that hydrogen sulfide generation has a potential therapeutic role in IR-induced cardiac hypertrophy and arrhythmia via amelioration of CX-43 expression and opening of K ATP channels. Keywords • Hydrogen sulfide • Cardiac hypertrophy • K ATP channels Bull. of Egyp. Soc. Physiol. Sci.

The Potential of Hydrogen Sulfide Donors in Treating Cardiovascular Diseases

“…Similarly, a recent study indicated that H 2 S-induced elevation of miR-133a results in the downstream regulation of the Ca 2+ /calcineurin/nuclear factors of activated T-cells pathway [ 162 ]. Furthermore, the treatment of a CH-induced rat model with NaHS markedly restores ventricular function by reducing the expression of connexin-43 and activating K ATP channels [ 163 ]. A recent study further shows that treatment with SG1002 can prevent Hcy-induced hypertrophy in CBS +/- mice and improve cardiac function by reducing MMP activity and TGF-β activation [ 164 ].…”