Deoxycorticosterone acetate salt hypertension in apolipoprotein E-/- mice results in accelerated atherosclerosis: the role of angiotensin II.
Previous studies have shown that administration of angiotensin II to atherosclerosis-prone animal models results in an increase in the extent of atherosclerosis and that this effect may be independent of changes in blood pressure. We sought to determine whether atherosclerosis was increased in the setting of a low renin model of hypertension. Apolipoprotein E-deficient mice were made hypertensive using the deoxycorticosterone acetate salt model. We found that this resulted in a dramatic increase in the atherosclerotic lesion area in the setting of either a low- or high-fat diet. In the hypertensive animals, we observed an increase in angiotensin II staining that was localized to the adventitial macrophages. The increase in atherosclerosis was inhibited by administration of an angiotensin receptor antagonist, an angiotensin-converting enzyme inhibitor, or a renin inhibitor. In addition, blood pressure reduction, with either a calcium channel blocker or hydralazine, reduced the extent of atherosclerosis indicating an important contribution of the mechanical effects of elevated blood pressure. These data suggest that, even in the setting of hypertension that is not associated with activation of the systemic renin-angiotensin system, local generation of angiotensin II within the arterial wall may be of pathophysiological relevance to the development of atherosclerosis.
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology; D001808:Blood Vessels / Q000378:metabolism; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced* / Q000150:complications* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012084:Renin-Angiotensin System; D012965:Sodium Chloride; D013997:Time Factors
D001057:Apolipoproteins E; D000804:Angiotensin II; D003900:Desoxycorticosterone; D012965:Sodium Chloride