Cardio- and reno-protective effects of candesartan compared to lisinopril in a rat model of cardiorenal syndrome type 4: implication of oxidative stress and inflammation.

Cardiorenal syndrome (CRS) is a progressive and life‑threatening disorder associated with high morbidity and mortality. This study aimed to compare the cardio‑ and reno‑protective effects of candesartan and lisinopril in a 5/6 nephrectomy model of type 4 CRS, with emphasis on their modulation of oxidative stress and inflammatory signaling pathways. Immediately after 5/6 subtotal nephrectomy, candesartan (10 mg/kg/day) or lisinopril (12.5 mg/kg/day) was administered by gastric gavage for 10 weeks. Serum urea and creatinine were measured 10 days post‑surgery. At the end of the treatment period, rats were euthanized, and blood, renal, and cardiac tissues were collected. Serum urea, creatinine, and cardiac BNP were quantified, along with renal and cardiac levels of SOD, MDA, NF‑κB, JAK‑2, STAT‑3, and TGF‑β. Histopathological examinations were also performed. Both candesartan and lisinopril significantly improved renal function, reduced arterial blood pressure, attenuated cardiac hypertrophy, lowered BNP levels, decreased renal and cardiac concentrations of MDA, NF‑κB, JAK‑2/STAT‑3, and TGF‑β, and increased SOD levels compared with the 5/6 nephrectomy group. Histopathological examination confirmed marked reductions in renal and cardiac tissue injury. Candesartan exerted greater reno‑protective effects than lisinopril in this model of CRS, whereas lisinopril offered slightly superior cardioprotective benefits. Both agents appear to mediate their therapeutic actions through attenuation of oxidative stress and inflammatory signaling.