Experimental and clinical data support the notion that
peroxisome proliferator-activated receptor γ (PPARγ) activation is associated with anti-
atherosclerosis as well as anti-diabetic effect.
Telmisartan, an
angiotensin receptor blocker (ARB), acts as a partial PPARγ agonist. We hypothesized that
telmisartan protects against
diabetic vascular complications, through PPARγ activation. We compared the effects of
telmisartan,
telmisartan combined with
GW9662 (a PPARγ antagonist), and
losartan with no PPARγ activity on
vascular injury in obese type 2 diabetic db/db mice. Compared to
losartan,
telmisartan significantly ameliorated vascular endothelial dysfunction, downregulation of phospho-eNOS, and coronary arterial remodeling in db/db mice. More vascular protective effects of
telmisartan than
losartan were associated with greater anti-inflammatory effects of
telmisartan, as shown by attenuation of vascular
nuclear factor kappa B (NFκB) activation and
tumor necrosis factor α. Coadministration of
GW9662 with
telmisartan abolished the above mentioned greater protective effects of
telmisartan against
vascular injury than
losartan in db/db mice. Thus, PPARγ activity appears to be involved in the vascular protective effects of
telmisartan in db/db mice. Moreover,
telmisartan, but not
losartan, prevented the downregulation of vascular PPARγ in db/db mice and this effect of
telmisartan was cancelled by the coadministration of
GW9662. Our data provided the first evidence indicating that PPARγ activity of
telmisartan contributed to the protective effects of
telmisartan against
diabetic vascular complication. PPARγ activity of
telmisartan was involved in the normalization of vascular PPARγ downregulation in diabetic mice. Thus,
telmisartan seems to exert vascular protective effects in hypertensive patients with diabetes.