The cardioprotective potential of valsartan in myocardial ischaemia reperfusion injury.

Abstract

BackgroundIschaemia/reperfusion injury describes the experimentally and clinically prevalent finding that tissue ischaemia with inadequate oxygen followed by successful reperfusion initiates a wide and complex array of inflammatory responses that may aggravate local injury as well as induce impairment of remote organ function by mechanisms that involve oxidative stress, inflammation, and apoptosis.ObjectiveThis study was undertaken to investigate the potential role of valsartan angiotensin receptor blocker-1 (ARB-1) in the amelioration of myocardial ischaemia/reperfusion injury induced by ligation of coronary artery in a rat model.Material and methodsAdult male Albino rats were randomised into four equal groups (seven rats in each group). In group 1 (sham group) the rats underwent the same anaesthetic and surgical procedure as the control group except for ligation of the left anterior descending (LAD) coronary artery; group 2 (control group) rats were subjected to regional ischaemia for 25 minutes by ligation of LAD coronary artery and reperfusion for 2 hours; group 3 (control vehicle group) rats received (normal saline) vehicle of valsartan via IP injection and were subjected to regional ischaemia for 25 minutes by ligation of LAD coronary artery and reperfusion for two hours; group 4 (valsartan treated group) rats were pretreated with valsartan 10 mg/kg IP 30 minutes before ligation of LAD coronary artery. At the end of the experiment, blood samples were taken by direct cardiac puncture for the measurement of plasma levels of troponin T (cTnT) and serum levels for both malondialdehyde MDA and glutathione GSH. After blood sampling, the heart was removed and divided into two parts; the apex was used for histopathological examination, and the remaining part was used for the measurement of cardiac tissue levels of tumour necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10), cysteine aspartic acid-protease 3 (caspase-3), and BCL2-associated X protein (BAX), after removal of the remaining blood clots and aorta.ResultsIn the active control group, as compared with the sham group, the results revealed that the myocardial tissue levels of inflammatory cytokines TNF-α, IL-6, IL-10, caspase-3, and BAX, and the plasma level of cTnT and serum level of malondialdehyde MDA were significantly increased (p < 0.001), while the serum level of glutathione GSH was significantly decreased (p < 0.001). Regarding the histopathological part of the study, all rats in the active control group showed a significant cardiac tissue injury (p < 0.001) compared with the sham group. Valsartan significantly counteracted (p < 0.001) the increase in the myocardial tissue levels of TNF-α, IL-6, caspase-3, and BAX; additionally, it counteracted the increase in plasma level of cTnT and serum level of malondialdehyde MDA, while valsartan produced highly significant elevation (p < 0.001) in the cardiac tissue level of IL-10 and serum level of glutathione GSH and significantly reduced (p < 0.001) the cardiac tissue injury in the valsartan pretreated rats.ConclusionsThe results of the present study reveal that valsartan ameliorates myocardial ischaemia reperfusion injury in rats by interfering with inflammatory reactions and apoptosis that are induced by ischaemia reperfusion injury.