Valsartan Protects in High Fat Diet During Ischemic Reperfusion Injury

Aim: The study investigates the effect of Valsartan, an Angiotensin II type 1 receptor blocker (ARB), on the blunted neuroprotective response of ischemic post-conditioning (iPoCo) in rats subjected to High Fat Diet (HFD). Background: The neuroprotective response of iPoCo is blunted in conditions of vascular endothelial dysfunction (ED) associated with hypercholesterolemia, diabetes, hypertension, etc. Objectives: The study was undertaken to investigate the effect of Valsartan, an ARB, on the blunted neuroprotective response of iPoCo in rats subjected to HFD. Methods: Wistar rats were subjected to HFD for 56 days. The cerebral ischemic injury was induced by bilateral common carotid artery occlusion (BCCAO) for 12 min followed by reperfusion of 24 hrs. iPoCo was induced by three preceding cycles of ischemia and reperfusion lasting 1 min each given immediately after BCCAO at the onset of prolonged reperfusion. The extent of the injury was assessed in terms of memory impairment using the Morris Water Maze test (MWM), sensorimotor disturbance using the neurological severity score (NSS), and cerebral infarct size using triphenyl tetrazolium chloride staining. Series of biochemical estimations including brain thiobarbituric acid reactive species (TBARS); reduced glutathione (GSH); myeloperoxidase (MPO); tumor necrosis factor-α (TNF-α); Nrf-2 and serum cholesterol, serum nitrite levels were performed. Results: BCCAO produced significant cerebral injury indicated by increased cerebral infarct size, memory impairment, increased NSS, and various biochemical alterations (increased cholesterol, TBARS, MPO, TNF-α, Nrf-2, and decreased nitrite and GSH levels). Significant neutrophil infiltration was also observed. iPoCo attenuated BCCAO-induced injury with respect to the above parameters in normal rats. The protective response of iPoCo was lost in HFD-treated rats. Treatment of Valsartan attenuated cerebral injury, potentiated the neuroprotective response of iPoCo in normal rats, and also restored the blunted neuroprotective effect of iPoCo in HFD-treated rats along with enhanced Nrf-2 levels. Conclusion: Valsartan exerted a neuroprotective effect by virtue of its multiple actions with a crucial role of Nrf2 activation.