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.
First Department of Internal Medicine, Showa University School of Medicine, Tokyo 142-8666, Japan.
Jianmin
J
Ran
Tsutomu
T
Hirano
Tomoyasu
T
Fukui
Kiyomi
K
Saito
Haruaki
H
Kageyama
Kenta
K
Okada
Mitsuru
M
Adachi
D052242:Adiponectin / Q000097:blood*; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005951:Glucose Tolerance Test; D006973:Hypertension / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D052242:Adiponectin; D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D001786:Blood Glucose; D007093:Imidazoles; D007328:Insulin; D020738:Leptin; D009842:Oligopeptides; D011725:Pyridines; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; C504339:adiponectin receptor 1, rat; D000804:Angiotensin II; C060894:CGP 42112A; C073402:PD 123319; C437965:olmesartan