Opposing actions of angiotensin II type 1 and 2 receptors on plasma cholesterol levels in rats.
OBJECTIVE
There have been very few studies to examine how angiotensin II (AII) affects lipid metabolism. We examined the roles of AII type 1 and type 2 receptors (AT1R and AT2R) in cholesterol metabolism in rats fed either normal chow or high-fructose diets.


RESULTS
AII (100 ng/kg per min) or vehicle (saline) was continuously infused through an osmotic mini-pump to normal chow-fed or 60% fructose-fed rats for 2 weeks. AII infusion markedly elevated both the systolic and diastolic blood pressure in the two animal groups. AII did not affect the plasma total cholesterol (TC) in the chow-fed rats. In the AII-infused rats treated with olmesartan medoxomil, an AT1R blocker, we were interested to observe significant decreases in plasma TC and non-high-density lipoprotein (HDL)-cholesterol (C) (TC minus HDL-C), and liver cholesterol content were also decreased. Simultaneous infusion of AII and PD123319, an AT2R blocker, markedly increased non-HDL-C and hepatic cholesterol. The infusion of CGP42112A, an AT2R agonist, decreased non-HDL-C by 30% in normal rats. The AII infusion led to significant elevations in TC and non-HDL-C in the fructose-fed rats, and olmesartan treatment completely rectified this AII-induced hypercholesterolemia.


CONCLUSIONS
These results suggest that the AII receptors exert opposing effects on the plasma cholesterol level; that is, AT1R increases plasma cholesterol while AT2R decreases it. Fructose feeding may selectively augment the action of AT1R and thereby enhance the increase in plasma cholesterol levels in response to AII infusion.
Hirano
Tsutomu
T
First Department of Internal Medicine, Showa University School of Medicine, Hatanodai, Tokyo, Japan. hirano@med.showa-u.ac.jp
Ran
Jianmin
J
Adachi
Mitsuru
M
D000804:Angiotensin II / Q000494:pharmacology*; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D000068557:Olmesartan Medoxomil; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology*; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D009842:Oligopeptides; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000804:Angiotensin II; C060894:CGP 42112A; C073402:PD 123319; D000068557:Olmesartan Medoxomil; D002784:Cholesterol