Inhibition of vascular angiotensin-converting enzyme by telmisartan via the peroxisome proliferator-activated receptor gamma agonistic property in rats.

The angiotensin receptor blocker (ARB) telmisartan is a partial agonist of peroxisome proliferator-activated receptor gamma (PPARgamma). Typical PPARgamma agonists suppress the gene expression of angiotensin-converting enzyme (ACE) in vascular tissues. However, it remains unclear whether or not PPARgamma activation by telmisartan can inhibit vascular ACE activity. We compared the effects of PPARgamma agonistic telmisartan and non-agonistic valsartan on ACE, vascular function and oxidative stress in stroke-prone spontaneously hypertensive rats (SHR-SP) and in sodium (1% NaCl)-loaded SHR-SP. SHR-SP and sodium-loaded SHR-SP received placebo, 1 mg/kg telmisartan, or 10 mg/kg valsartan for 2 weeks. Systolic blood pressure (SBP) was equally reduced in SHR-SP given either telmisartan or valsartan compared with SHR-SP given placebo. However, neither telmisartan nor valsartan suppressed SBP in sodium-loaded SHR-SP. Acetylcholine induced significantly less vasorelaxation in SHR-SP than in Wistar-Kyoto rats, but telmisartan and valsartan each significantly prevented such vasorelaxation. However, telmisartan significantly attenuated acetylcholine-induced vasorelaxation in sodium-loaded SHR-SP, whereas valsartan did not. Telmisartan significantly attenuated NADPH oxidase subunit p22(phox) gene expression in both SHR-SP and sodium-loaded SHR-SP, whereas valsartan did not. Likewise, telmisartan also significantly attenuated the significantly increased vascular ACE activity in sodium-loaded SHR-SP, whereas valsartan did not. In conclusion, the partial PPARgamma agonist telmisartan might inhibit vascular ACE activity, and result in the prevention of oxidative stress and endothelial dysfunction more effectively than non-agonistic valsartan.