ASSOCIATION OF BLOOD-PRESSURE VARIABILITY WITH INDUCTION OF ATHEROSCLEROSIS IN CHOLESTEROL-FED RATS

The influence of increased lability of blood pressure on the developme nt of aortic atherosclerosis was examined. Because sinoaortic denervat ion (SAD) produced increased lability of blood pressure without blood pressure elevation, the development of atheromatous plaque was examine d in SAD rats. These rats were fed a high-cholesterol diet and were de nuded of endothelium so that development of atherosclerosis was accele rated. Five groups of male Wistar rats were used: A) controls, B) high -cholesterol diet (HC), C) HC + denudation (DN), D) HC + DN + renal ar tery clipping (2K1C), and E) HC + DN + sinoaortic denervation (SAD). D enudation was accomplished by scraping the aortic lumen with a balloon catheter, and hypertension was induced by clipping the left renal art ery. After recording blood pressure and heart rate for 6 weeks, the ra ts were killed, blood samples were collected, and thoracic aortas were removed for pathologic examination. All the groups of rats fed a high -cholesterol diet developed marked hypercholesterolemia and hypotrigly ceridemia. High-cholesterol diet alone could not induce aortic atheros clerosis, whereas aorta of HC + DN rats showed slight intimal thickeni ng with smooth muscle cell proliferation. On the other hand, aorta of HC + DN + 2K1C rats showed marked atheromatous plaque with prominent c ellular proliferation, and aorta of SAD rats also showed mild to moder ate atheromatous plaque. Accordingly, we concluded that increased vari ability in circadian blood pressure per se, as well as hypertension, c ould induce aortic atherosclerosis in the hypercholesterolemic and end othelium-denuded rats.