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 (All) affects lipid metabolism. We examined the roles of All type 1 and type 2 receptors (AT1R and AT2R) in cholesterol metabolism in rats fed either normal chow or high-fructose diets. Methods and results All (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. All infusion markedly elevated both the systolic and diastolic blood pressure in the two animal groups. All did not affect the plasma total cholesterol (TC) in the chow-fed rats. In the All-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 All 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 All infusion led to significant elevations in TC and non-HDL-C in the fructose-fed rats, and olmesartan treatment completely rectified this All-induced hypercholesterolemia. Conclusions These results suggest that the All 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 All infusion.