title: Angiotensin II receptor blockers decrease serum concentration of fatty acid-binding protein 4 in patients with hypertension.
abstract: Elevated circulating fatty acid-binding protein 4 (FABP4/A-FABP/aP2), an adipokine, is associated with obesity, insulin resistance, hypertension and cardiovascular events. However, how circulating FABP4 level is modified by pharmacological agents remains unclear. We here examined the effects of angiotensin II receptor blockers (ARBs) on serum FABP4 level. First, essential hypertensives were treated with ARBs: candesartan (8 mg day(-1); n=7) for 2 weeks, olmesartan (20 mg day(-1); n=9) for 12 weeks, and valsartan (80 mg day(-1); n=94) or telmisartan (40 mg day(-1); n=91) for 8 weeks added to amlodipine (5 mg day(-1)). Treatment with ARBs significantly decreased blood pressure and serum FABP4 concentrations by 8-20% without significant changes in adiposity or lipid variables, though the M value determined by hyperinsulinemic-euglycemic glucose clamp, a sensitive index of insulin sensitivity, was significantly increased by candesartan. Next, alterations in FABP4 secretion from 3T3-L1 adipocytes were examined under several agents. Lipolytic stimulation of the β-adrenoceptor in 3T3-L1 adipocytes by isoproterenol increased FABP4 secretion, and conversely, insulin suppressed FABP4 secretion. However, treatment of 3T3-L1 adipocytes with angiotensin II or ARBs for 2 h had no effect on gene expression or secretion of FABP4 regardless of β-adrenoceptor stimulation. In conclusion, treatment with structurally different ARBs similarly decreases circulating FABP4 concentrations in hypertensive patients as a class effect of ARBs, which is not attributable to blockade of the angiotensin II receptor in adipocytes. Reduction of FABP4 levels by ARBs might be involved in suppression of cardiovascular events.
authors: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Masato
authors: M
authors: Furuhashi
authors: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Tomohiro
authors: T
authors: Mita
authors: Department of Nephrology, Teine Keijinkai Hospital, Sapporo, Japan.
authors: Norihito
authors: N
authors: Moniwa
authors: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Kyoko
authors: K
authors: Hoshina
authors: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Shutaro
authors: S
authors: Ishimura
authors: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Takahiro
authors: T
authors: Fuseya
authors: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Yuki
authors: Y
authors: Watanabe
authors: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Hideaki
authors: H
authors: Yoshida
authors: Sapporo Medical University, Sapporo, Japan.
authors: Kazuaki
authors: K
authors: Shimamoto
authors: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Tetsuji
authors: T
authors: Miura
mesh_terms: D016475:3T3 Cells; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D017311:Amlodipine / Q000627:therapeutic use; D057912:Angiotensin II Type 2 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D050556:Fatty Acid-Binding Proteins / Q000097:blood*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D007545:Isoproterenol / Q000494:pharmacology; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008875:Middle Aged
chemical_list: D000318:Adrenergic beta-Agonists; D057912:Angiotensin II Type 2 Receptor Blockers; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D008055:Lipids; D017311:Amlodipine; D007545:Isoproterenol