title: Effects of telmisartan and olmesartan on insulin sensitivity and renal function in spontaneously hypertensive rats fed a high fat diet.
abstract: Although telmisartan, an angiotensin II receptor blocker (ARB), has an agonistic action for proliferator-activated receptor (PPAR)-γ in vitro, it remains to be determined whether telmisartan exerts such an action in vivo using a non-toxic dose (<5 mg/kg in rats). To address the issue, telmisartan (2 mg/kg) and olmesartan (2 mg/kg), another ARB without PPAR-γ agonistic action, were given to spontaneously hypertensive rats (SHR) fed a high fat diet (HFD). HFD decreased plasma adiponectin, and caused insulin resistance, hypertriglyceridemia and renal damage, which were improved by ARBs. Protective effects of telmisartan and olmesartan did not significantly differ. In addition, in vitro study showed that 1 μM of telmisartan did not elevate the mRNA expression of adipose protein 2, which is a PPAR-γ-stimulated adipogenic marker gene, in preadipocytes with 3% albumin. To obtain 1 μM of plasma concentration, oral dose of telmisartan was calculated to be 6 mg/kg, which indicates that PPAR-γ agonistic action is negligible with a non-toxic dose of telmisartan (<5 mg/kg) in rats. This study showed that 2 mg/kg of telmisartan and olmesartan ameliorated insulin resistance, hypertriglyceridemia and renal damage in SHR fed a HFD. As beneficial effects of telmisartan and olmesartan did not significantly differ, these were mediated through the PPAR-γ-independent actions.
authors.affiliation: Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi, 329-0498, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Yanagihara
authors.affiliation: Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi, 329-0498, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ushijima
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Nippon Medical University, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Arakawa
authors.affiliation: Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi, 329-0498, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Aizawa
authors.affiliation: Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi, 329-0498, Japan. Electronic address: akiofuji@jichi.ac.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D059305:Diet, High-Fat; D007093:Imidazoles / Q000494:pharmacology*; D007333:Insulin Resistance; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D051379:Mice; D051381:Rats; D011918:Rats, Inbred SHR; D000077333:Telmisartan; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D007093:Imidazoles; D013777:Tetrazoles; C437965:olmesartan; D000077333:Telmisartan
keywords: Angiotensin II receptor blocker; Olmesartan; Proliferator-activated receptor-γ; SHR fed a high fat diet; Telmisartan