Endothelin receptor blocker bosentan inhibits hypertensive cardiac fibrosis in pressure overload-induced cardiac hypertrophy in rats

Aim The aim of this study was to investigate the effect of bosentan (25, 50, 100 mg/kg) on left ventricular contractile function, cardiac fibrosis, and oxidative stress in pressure overload-induced cardiac hypertrophy in rats. Methods Male rats (200–250 g) were assigned into various groups, namely, sham, aortic constriction, aortic constriction+bosentan (25, 50, and 100 mg/kg), and sham+bosentan (100 mg/kg). Myocardial hypertrophy was produced by constriction of the abdominal aorta. Four weeks after treatment with bosentan (25, 50, and 100 mg/kg perorally), the left ventricular contractile function was measured using a Millar catheter and ECG was carried out. Results Treatment with bosentan (50 and 100 mg/kg perorally) significantly and dose-dependently (P<0.01 and <0.001) restored hemodynamic parameters including ECG, blood pressure, and left ventricular function. It also significantly elevated the levels of biochemical markers (P<0.001), that is, superoxide dismutase, reduced glutathione, and membrane-bound inorganic phosphate enzymes like Na+–K+-ATPase and Ca2+-ATPase. The elevated levels of creatine kinase-MB and lactate dehydrogenase enzymes, as well as the activities of malondialdehyde and tumor necrosis factor-α, were significantly attenuated (P<0.05 and <0.001) by bosentan (50 and 100 mg/kg perorally) treatment. An upregulation in the mRNA expression of endothelin-1 was significantly (P<0.05 and <0.001) attenuated by bosentan (50 and 100 mg/kg perorally) treatment. Histological aberration induced after pressure overload was restored by bosentan treatment. Conclusion Bosentan attenuates the development of cardiac hypertrophy by blocking the endothelin-1 receptor and improving left ventricular function; it also ameliorates endogenous biomarkers in pressure overload-induced cardiac hypertrophy in rats.