Effects of candesartan on cellular redox status and bioenergetics of cardiac tissue in normal and chronically stressed rats

Background Studies of redox status and bioenergetics in cardiac tissue during unpredictable chronic mild stress (UCMS) are scarce. The present study examined the effect of candesartan, an angiotensin II type 1 receptor (AT1R) blocker primarily used to treat hypertension and congestive heart failure, on the antioxidant capacity and energy homeostasis of cardiac tissue in UCMS-subjected rats. Methods Forty-eight male Wistar rats were randomly assigned to four groups (n = 12/group): undosed normal controls (NC), UCMS-subjected rats (UCMS), unstressed candesartan-treated rats (Can), and stressed candesartan-treated rats (UCMS + Can). Enzyme activities and mRNA transcripts of key antioxidant enzymes, tricarboxylic acid cycle enzymes, and respiratory chain complexes were measured in myocardial tissue, together with oxidative-phosphorylation (OXPHOS) markers, redox state, and the energy-homeostasis ratios GSH/GSSG, NAD + /NADH, and ATP/ADP. Results The UCMS group showed marked elevations in oxidative-stress markers, accompanied by significantly reduced antioxidant enzyme activities and downregulated antioxidant gene expression. In parallel, all TCA-cycle and OXPHOS enzyme activities were significantly decreased, and their relative gene transcripts were markedly downregulated. The cellular GSH/GSSG and ATP/ADP ratios were significantly lowered, whereas the NAD + /NADH ratio was increased. Each of these changes was either fully reversed or significantly attenuated in unstressed and stressed rats receiving candesartan. Conclusion Candesartan clearly mitigates cellular oxidative stress and the disruption of energy metabolism in the myocardial tissue of UCMS-subjected rats. Because blood pressure, cardiac function and systemic haemodynamics were not measured, these findings should be interpreted as biochemical evidence of a cytoprotective action of AT1R blockade in myocardial tissue, and they provide a preliminary rationale for further evaluation of candesartan in stress-related cardiovascular disorders.