Ang II Infusion at 8, But not at 16 Weeks Age, Promotes Atherosclerosis in ApoE-Deficient Mice
Although hypertension has long been regarded as a risk factor for atherosclerosis, the pathophysiologic mechanism is unknown. Angiotensin II can affect almost every step in the development of atherosclerosis. A number of recent studies show that angiotensin blockade reduces, and angiotensin infusion enhances atherogenesis in hyperlipidemic, ApoE-deficient mice. However, the relative importance and the time course of the processes involved remains to be elucidated. In the present study, we examined the effects of Ang II on the development of aortic root atherosclerosis in male ApoE-deficient mice. Osmotic minipumps containing saline or Ang II were implanted subcutaneously in 8 or 16 week old mice. Ang II was infused at a rate of 1000 ng/kg/min for 28 days. In all mice infused with Ang II, systolic blood pressure (SBP) measured by tail cuff increased significantly. Accordingly, plasma renin concentration (PRC) in these mice was suppressed to virtually zero. In mice in which infusion was commenced at 16 weeks age there was no increase in atherosclerotic lesion area. However, in mice in which the infusion was commenced at 8 weeks age, lesion area increased 2.3-fold (p<0.05, unpaired t-test). Total and HDL cholesterol levels were unaffected by Ang II treatment. Although, in the 16-week-old animals, there was considerable atherosclerosis, it had not reached maximum levels. Taken together, these observations suggest that Ang II may have its greatest effects on lesion initiation.