Cardiovascular responses to angiotensin II in atherosclerosis

Abstract

Atherosclerosis is associated with increased angiotensin II AT1-receptor expression and vascular hyperresponsiveness to angiotensin II. Nevertheless, atherosclerosis is often not accompanied by hypertension. We studied if the hypertensive effect of angiotensin II is more pronounced in atherosclerosis. Rabbits were fed a high-cholesterol diet (n = 10) for 12 weeks, followed by a standard diet for another 6 weeks. Control animals received the standard diet (n = 8) for 18 weeks. After 18 weeks, haemodynamic measurements were performed during a baseline recording and during an intravenous infusion of angiotensin II (0.4 microg kg-1 min-1). Atherosclerosis in the high-cholesterol group was verified by histological and lipidchemical tissue examinations. During angiotensin II infusion, total peripheral resistance (TPR) increased more in the high-cholesterol group than in controls (+81.6 +/- 12.4 vs. +40.6 +/- 9.7 mmHg min L-1, P < 0.05). While cardiac output and stroke volume (SV) decreased more in the high-cholesterol group (P < 0.05), reflex bradycardia was stronger in the control group (P < 0.05), indicating a reduced baroreceptor reflex sensitivity in atherosclerosis. Despite the larger increase in TPR and the reduced baroreceptor reflex sensitivity in the high-cholesterol group, maximum blood pressure response to angiotensin II was similar in both groups. The lack of a greater blood pressure response to angiotensin II in the high-cholesterol group could be the result of the early stages of heart failure. Under resting conditions, heart failure seems to be fully compensated, as baseline haemodynamic parameters were similar in the high-cholesterol group and in controls. However, during angiotensin II infusion, the compensatory mechanisms do not prevent a stronger fall in cardiac output and SV. Therefore, the blood pressure response to angiotensin II is not exaggerated in atherosclerotic animals, as vascular hyperresponsiveness to angiotensin II is opposed by the stronger fall in cardiac output and SV.

Association Between Atherosclerotic Aortic Plaques and Left Ventricular Hypertrophy in Patients With Cerebrovascular Events

“…33 Other than its important role in LV remodeling, 30 -34 angiotensin II actively participates in atherogenesis. [22][23][24][25][26][27][28][29] It is well known that circulating monocytes containing angiotensinconverting enzyme (ACE) can penetrate the vascular wall after endothelial dysfunction and/or damage. Those cells transform themselves into foam cells containing ACE, which provokes local synthesis of angiotensin II.…”

“…Evidence from the literature [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] indicates that the development of atherosclerotic lesions and myocardial remodeling share common pathological mechanisms. If this assumption is correct, it is reasonable to hypothesize that structural cardiac alteration indicating remodeling could be associated with the presence of atherosclerotic plaque of the aorta in patients seized by CVE.…”