title: Telmisartan protects against vascular dysfunction with peroxisome proliferator-activated receptor-γ activation in hypertensive 5/6 nephrectomized rats.
abstract: OBJECTIVE
  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 (Ser(1177)) 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.
  
  
  CONCLUSIONS
  Telmisartan exhibited vasoprotection via PPAR-γ agonistic properties in hypertensive CKD rats.
authors.affiliation: Department of Clinical Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Hiroe
authors.initials: H
authors.lastname: Toba
authors.forename: Jiahong
authors.initials: J
authors.lastname: Wang
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohigashi
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kobara
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nakata
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D054333:Drug Partial Agonism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077333:Telmisartan; D014664:Vasodilation / Q000187:drug effects
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D047228:Angiotensin II Type 1 Receptor Blockers; D000813:Anilides; D001562:Benzimidazoles; D001565:Benzoates; D047495:PPAR gamma; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019808:Losartan; D000077333:Telmisartan