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

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 microg/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 alpha 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 microg/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.