Frontiers in pharmacology · 2026
Effects of candesartan on cellular redox status and bioenergetics of cardiac tissue in normal and chronically stressed rats.
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Abulmeaty Mahmoud M A, Ghneim Hazem K, Aldisi Dara, Wahid Reham M, Ashour Wesam M R, Giesy John P, Aboul-Soud Mourad A M
Аннотация
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.
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.