Effect of hypotension on atherogenesis and aortic wall composition.

Cynomolgus monkeys with a stable, midthoracic aortic coarctation producing at least a pressure gradient of 10 mm Hg were fed an atherogenic diet containing 2% cholesterol and 25% peanut oil for 6 months. Standard, anatomically defined segments of thoracic aorta above and below the coarctation and of abdominal aorta were then compared to corresponding segments from atherogenie diet and normal diet control animals with respect to mural cholesterol, elastin, collagen, and DNA content and percentage surface atherosclerosis. Atherosclerotic lesions occupied 74 + 8% of the intimal surface above the coarctations and 56 2 7% of the corresponding surface in atherogenic diet controls, but the difference was not statistically significant. Upper thoracic mural cholesterol content was the same for the two groups. Atherosclerotic lesions were strikingIy less prominent below coarctations occupying only 12 2 4% of the distal thoracic intimal surface compared to 54 2 9% in atherogenic diet controls (P < 0.001) and only 10 -+ 3% of the abdominal intimal surface compared to 56 ? 14% in atherogenic diet controls (P < 0.001). Mural cholesterol content below the coarctation was the same as in normal diet control animals. Distal to the coarct, DNA and collagen content were reduced, suggesting that lowered pressure resulted in increased collagen degradation and decreased cellularity. Despite the absence of persistent hypertension above the coarctation, the upper thoracic aorta contained more elastin than controls but DNA content was normal. The results indicate that even a small reduction in blood pressure below normal levels has a marked inhibiting effect on the induction of diet-induced lesions. The associated reduction in cellularity and the low level of mural cholesterol content suggest that mural lipid accumulation, cell proliferation, and lesion formation are dependent on the presence of normal or elevated blood pressure. High levels of circulating serum lipids are a necessary but insufficient condition for the development of experimental atherosclerosis.