EFFECT OF CAPTOPRIL AND LOSARTAN ON BLOOD-PRESSURE AND ACCUMULATION OF LDL AND FIBRINOGEN BY AORTIC-WALL AND OTHER TISSUES IN NORMOTENSIVE AND HYPERTENSIVE RATS

Hypertension, low-density lipoprotein (LDL), and fibrinogen are risk f actors for atherosclerosis. We investigated the effect of reducing blo od pressure, by blocking the renin-angiotensin system (RAS), on the ac cumulation of these atherogenic proteins in arterial walls and other t issues in conscious, unrestrained, normotensive and hypertensive rats. The accumulation of LDL and fibrinogen, labeled respectively with I-1 25 and [I-131], the adduct tyramine cellobiose ([I-125]-TC-LDL and [I- 131]-TC-fibrinogen) was compared in aortic walls, heart, lung, skeleta l muscle, liver, kidney, and adrenal gland during the final 24 h of tr eatment with either the angiotensin-converting enzyme (ACE) inhibitor captopril or the angiotensin II-receptor I (AT(1)) antagonist losartan . In normotensive rats, the blood pressure was decreased only by losar tan. In spontaneously hypertensive rats (SHRs), the blood pressure was decreased by both losartan and captopril. Captopril had no significan t effect on the accumulation of LDL or fibrinogen by the aortic wall. Losartan significantly increased the accumulation of LDL by the aortic wall of SHRs. Neither agent produced any change in LDL or fibrinogen accumulation in any of the other tissues. These results indicate that although blocking the RAS at either the enzymic or receptor level prod uces significant decrease of blood pressure in hypertensive animals, o nly losartan has any affect on LDL accumulation by the aortic wall.