Angiotensin II infusion decreases plasma adiponectin level via its type 1 receptor in rats: an implication for hypertension-related insulin resistance

• Published in: Metabolism, clinical and experimental clinical and experimental, 2006-04, Vol.55 (4), p.478-488
• Main Authors: Ran, Jianmin, Hirano, Tsutomu, Fukui, Tomoyasu, Saito, Kiyomi, Kageyama, Haruaki, Okada, Kenta, Adachi, Mitsuru
• Format: Article
• Language: English
• Subjects: Adiponectin - blood; Angiotensin II - administration & dosage; Angiotensin II - pharmacology; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin II Type 2 Receptor Blockers; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Glucose - analysis; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Dose-Response Relationship, Drug; Glucose Tolerance Test; Hypertension - physiopathology; Imidazoles - pharmacology; Injections, Subcutaneous; Insulin - blood; Insulin Resistance; Leptin - blood; Male; Medical sciences; Metabolic diseases; Oligopeptides - pharmacology; Pyridines - pharmacology; Rats; Rats, Wistar; Receptors, Adiponectin; Receptors, Cell Surface - metabolism; Tetrazoles - pharmacology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2005.10.009

We explored the mechanisms underlying the close association between hypertension and insulin resistance by measuring the changes in the plasma levels of adiponectin, a novel insulin sensitizer secreted by adipose tissue, in rats infused with angiotensin II (AII). Angiotensin II (100 ng/kg per minute) was subcutaneously infused with osmotic minipumps for 2 weeks in rats fed with either standard chow or a high-fructose diet. Insulin sensitivity index (SI) was assessed by the minimal model of Bergman [ Diabetes 1989;38:1512-27]. Angiotensin II infusion significantly increased blood pressure and decreased SI. Angiotensin II decreased plasma adiponectin levels from 3.7 to 2.9 μg/mL ( P < .01) without affecting the expression of adiponectin messenger RNA in adipose tissue. Angiotensin II infusion did not affect plasma leptin and tumor necrosis factor α levels. An AII type 1 receptor blocker, olmesartan, restored the low adiponectinemia induced by the AII infusion (50 ng/kg per minute). Plasma adiponectin levels were significantly lower in fructose-fed rats (2.3 μg/mL) than in chow-fed rats. Angiotensin II induced no further decrease of adiponectin, whereas olmesartan increased adiponectin remarkably both with and without AII infusion. The AII type 2 receptor blocker PD123319 left the AII-induced hypoadiponectinemia unchanged in both chow- and fructose-fed rats. The AII type 2 receptor agonist CGP42112A also left the adiponectin unchanged. Plasma adiponectin levels were substantially correlated with SI ( r = 0.61, P < .0001). These results suggest that AII suppresses adiponectin production via AII type 1 receptor, resulting in impaired insulin sensitivity.