Telmisartan Protects against Vascular Dysfunction with Peroxisome Proliferator-Activated Receptor-γ Activation in Hypertensive 5/6 Nephrectomized Rats

Abstract

Background/Aims: Telmisartan and losartan, angiotensin II type 1 (AT₁) receptor antagonists, are used to manage hypertension. We previously reported that telmisartan, a partial agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ), exhibited stronger vasoprotection than the same dose of losartan in normotensive chronic kidney disease (CKD) rats. We investigated whether telmisartan could inhibit vascular dysfunction in hypertensive CKD rats, via both AT₁ receptor blockade and PPAR-γ activation, more effectively than losartan, which decreased blood pressure to a similar extent as telmisartan. Methods: Two or three branches of the left renal artery were ligated and the right kidney was removed to make hypertensive CKD rats. Telmisartan (5 mg/kg), losartan (10 mg/kg) or telmisartan plus the PPAR-γ antagonist GW9662 was administered. Results: Blood pressure was increased in CKD rats. Telmisartan and losartan decreased blood pressure to the same levels. Impaired endothelium-dependent vasodilation, hyperplasia and decreased phospho-eNOS (Ser¹¹⁷⁷) expression in CKD rat aortas were improved by telmisartan. The aortic infiltration by macrophages and expression of osteopontin were enhanced in CKD rats and suppressed by telmisartan. GW9662 partly canceled the normalization of vascular dysfunction. While losartan attenuated vascular changes, the extent of this attenuation was greater in the telmisartan-treated group. Conclusion: Telmisartan exhibited vasoprotection via PPAR-γ agonistic properties in hypertensive CKD rats.