Anti-Fibrotic Effect of Irbesartan via Attenuation of Endoplasmic Reticulum stress in Isoprenaline-Induced Myocardial Fibrosis

Background: Angiotensin receptor blockers are the new class of compounds used for the treatment of fibrotic diseases. Objectives: The purpose of this study was to investigate cardioprotective effect of irbesartan in isoproterenol induced endoplasmic reticulum stress, which results in myocardial fibrosis. Materials and Methods: Thirty wistar rats were assigned to study, 6 rats in a group. Myocardial fibrosis was induced by isoproterenol (5 mg/kg, s.c. for 15 days) which can cause cardiac toxicity. Irbesartan (10, 20 and 30 mg/kg, p.o.) was administered for 15 days after administration of isoproterenol. Post-treatment with irbesartan, cardiac functional measurements and the left and right ventricular weight indices were analyzed. Pathological alteration of levels of soluble collagen was determined. Results: The administration of irbesartan resulted in a significant (p<0.01) improvement in cardiac function and reduced levels of soluble collagen. Irbesartan also showed decrease in the level of malondialdehyde and an increase in defensive antioxidant enzymes (SOD, CAT, and GSH) thus, exerts antioxidant activity. Conclusion: Irbesartan possesses anti-fibrotic activity and offers protection against myocardial fibrosis, due to regulation of angiotensin II activity through blockade of AT 1 receptors which might attenuate the endoplasmic reticulum stress and thus inhibit myocardial fibrosis via inhibition of oxidative stress. The regulation of antioxidant defensive enzymes may be involved in anti-fibrotic effect of irbesartan.