title: Improved insulin sensitivity by the angiotensin II-receptor blocker losartan is not explained by adipokines, inflammatory markers, or whole blood viscosity.
abstract: We have previously found improved insulin sensitivity after antihypertensive treatment with an angiotensin II-receptor blocker as compared with a calcium channel blocker in hypertensives. In this study, we compare the effect of these 2 principal different vasodilating agents on levels of adipokines, inflammatory variables, and whole blood viscosity in the same hypertensive patients with cardiovascular risk factors. We test whether potential differences in these variables might explain the difference seen in insulin sensitivity. Twenty-one hypertensive patients (11 women, 10 men) with mean age of 58.6 years and blood pressure of 160 +/- 3/96 +/- 2 mm Hg entered a 4-week run-in period with open-label amlodipine 5 mg. Thereafter, they were randomized double-blindly to additional treatment with amlodipine 5 mg or losartan 100 mg; and after 8 weeks of treatment, all patients underwent laboratory testing. After a 4-week washout phase with open-label treatment, the participants were crossed over to the opposite treatment regimen for 8 weeks before final examination. No significant differences were seen in the blood levels of adiponectin (7814 +/- 870 vs 8090 +/- 967 ng/mL), leptin (961 +/- 122 vs 965 +/- 147 pmol/L), resistin (11.7 +/- 1.0 vs 11.3 +/- 0.7 ng/mL), plasminogen activator inhibitor 1 activity (23.9 +/- 2.2 vs 25.1 +/- 2.2 U/mL), tumor necrosis factor alpha (1.35 +/- 0.11 vs 1.72 +/- 0.28 pg/mL), and high-sensitivity C-reactive protein (3.09 +/- 0.84 vs 2.09 +/- 0.42 mg/L) between treatment with amlodipine 10 mg or losartan 100 mg + amlodipine 5 mg, respectively. Although no significant differences in whole blood viscosity and blood pressure were observed between the 2 treatment regimens, a consistent trend toward lower viscosity was found at all shear rates as vasodilatory treatment was intensified (baseline to amlodipine 5 mg to amlodipine 10 mg to losartan 100 mg + amlodipine 5 mg). Our data do not support that effects on adipokines, inflammatory markers, and whole blood viscosity could explain improved insulin sensitivity seen on AT1-receptor blockade.
authors.affiliation: Department of Cardiology, Cardiovascular and Renal Research Center, Ullevaal University Hospital, N-0407 Oslo, Norway. tonjeamb.aksnes@ulleval.no
authors.forename: Tonje Amb
authors.initials: TA
authors.lastname: Aksnes
authors.forename: Ingebjörg
authors.initials: I
authors.lastname: Seljeflot
authors.forename: Peter A
authors.initials: PA
authors.lastname: Torjesen
authors.forename: Aud
authors.initials: A
authors.lastname: Höieggen
authors.forename: Andreas
authors.initials: A
authors.lastname: Moan
authors.forename: Sverre E
authors.initials: SE
authors.lastname: Kjeldsen
mesh_terms: D054392:Adipokines / Q000097:blood*; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007333:Insulin Resistance; D019808:Losartan / Q000494:pharmacology*; D008875:Middle Aged; D014783:Viscosity
chemical_list: D054392:Adipokines; D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D019808:Losartan