EFFECT OF ANGIOTENSIN-II AND ENALAPRIL ON TRANSFER OF LOW-DENSITY-LIPOPROTEIN INTO AORTIC INTIMA IN RABBITS

To assess the mechanism behind a possible atherosclerosis-promoting ef fect of angiotensin II, the influence of angiotensin II, noradrenaline , and enalapril on transfer of low-density lipoprotein (LDL) into the arterial wall was investigated in conscious rabbits. Intravascular inf usion of angiotensin II (1.4 mu g/kg per minute) initially increased t he mean blood pressure from 70 to 80 mm Hg to 125 to 150 mmHg; this ef fect was transient, and the blood pressure returned to baseline values within 2 hours, despite continuous infusion of angiotensin II. The no rmalized influx of LDL into the aortic intima, determined after in viv o exposure to I-125-LDL for 1 hour, was 88+/-17 (n=6), 12+/-12 (n=5), and 28+/-6 (n=5) nL/cm(2) per hour (mean+/-SEM) during angiotensin II infusion at high blood pressure, during angiotensin II infusion after the blood pressure had been normalized, and during continuous saline i nfusions, respectively (P<.05 for high blood pressure versus low blood pressure and saline). When noradrenaline was used to increase blood p ressure to a level similar to that induced by angiotensin II, the norm alized influx of LDL in noradrenaline-treated rabbits was also increas ed markedly. Production of endogenous angiotensin II was inhibited wit h enalapril (2.9 mg/kg per day). Compared with placebo rabbits, enalap ril-treated rabbits had a 92% lower plasma angiotensin-converting enzy me activity and a 23% lower blood pressure. The normalized influx of L DL, however, was similar in the two groups at 18+/-2 (n=10) and 20+/-3 (n=10) nL/cm(2) per hour, respectively. These results suggest that an giotensin II increases the flux of the atherogenic LDL particle from p lasma into the arterial wall and that the effect is mediated in large part via increased blood pressure rather than through a direct effect on endothelial permeability.