Aggravation of atherosclerosis by hypertension in a subhuman primate model with coarctation of the aorta.

The interrelationships between hypertension and atherosclerosis were investigated in a subhuman primate model (cynomolgus monkey) with hypertension produced by surgically coarcting the miathoracic aorta. The hypertensive coarcted monkey fed a low cholesterol diet for 6 months did not develop complicating atherosclerosis but did develop focal intimal lesions as well as marked thickening of the musculoelastic media of both the large and small arteries. Fibrocellular thickening of the intima and media occurred in the vessels proximal to the coarctation but not distal to the coarctation suggesting that a high level of blood pressure with resulting increase in arterial wall tension is responsible for these changes. The hypertensive coarcted monkey fed a hypercholesterolemic diet (2% cholesterol and 10% butter) for 6 months developed severe coronary atherosclerotic disease with fibrous plaque formation. The disease produced over 65% luminal narrowing of the major coronary arteries and their extramural and intramural branches. In contrast the noncoarcted normotensive animal fed the same diet developed mild atherosclerosis of only the major coronary arteries which caused an average luminal narrowing of 12%. Aggravation of atherosclerosis by hypertension also appeared to occur in the other arteries above the coarctation particularly the cerebral arteries. When the hypertensive coarcted monkey with preestablished coronary atherosclerosis was treated with a low cholesterol diet and a combination of antihypertensive drugs (hydrochlorothiazide, hydralazine, and reserpine), the progression of the disease was arrested. There also was evidence that treatment caused some regression of the coronary lesions which appeared to "heal" by fibrosis. The treatment of both hyperlipidemia and hypertension appeared to be more effective than the treatment of hyperlipidemia, alone.