Pair-Feeding Differentiates Feed-Dependent and Pharmacodynamic Effects of Telmisartan in Wistar Rats

Telmisartan, an angiotensin II receptor blocker with partial PPAR-γ agonist activity, exhibits pleiotropic effects beyond its antihypertensive action, including modulation of lipid metabolism, erythropoiesis, and renal function. However, its anorexigenic properties complicate interpretation of systemic outcomes in toxicology studies. This study employed a pair-feeding design to differentiate feed-dependent effects from direct pharmacodynamic actions in male Wistar rats treated with telmisartan (100 mg/kg/day) for 28 days. Both telmisartan and pair-fed groups showed reduced body weight and hepatic triglyceride levels, confirming feed-dependent metabolic effects. In contrast, telmisartan-specific changes included suppression of erythroid indices; reduced serum triglycerides; elevated urea, creatinine, potassium, and inorganic phosphate levels; and mild gastric submucosal inflammation, none of which were observed in pair-fed controls. These findings demonstrate that telmisartan's hematological, renal, and lipid-lowering effects are feed-independent and mechanistically distinct from caloric restriction.