Association of blood pressure variability with induction of atherosclerosis in cholesterol-fed rats.

The influence of increased lability of blood pressure on the development of aortic atherosclerosis was examined. Because sinoaortic denervation (SAD) produced increased lability of blood pressure without blood pressure elevation, the development of atheromatous plaque was examined in SAD rats. These rats were fed a high-cholesterol diet and were denuded of endothelium so that development of atherosclerosis was accelerated. Five groups of male Wistar rats were used: A) controls, B) high-cholesterol diet (HC), C) HC+denudation (DN), D) HC+DN+renal artery clipping (2K1C), and E) HC+DN+sinoaortic denervation (SAD). Denudation was accomplished by scraping the aortic lumen with a balloon catheter, and hypertension was induced by clipping the left renal artery. After recording blood pressure and heart rate for 6 weeks, the rats 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 hypotriglyceridemia. High-cholesterol diet alone could not induce aortic atherosclerosis, whereas aorta of HC+DN rats showed slight intimal thickening with smooth muscle cell proliferation. On the other hand, aorta of HC+DN + 2K1C rats showed marked atheromatous plaque with prominent cellular proliferation, and aorta of SAD rats also showed mild to moderate atheromatous plaque. Accordingly, we concluded that increased variability in circadian blood pressure per se, as well as hypertension, could induce aortic atherosclerosis in the hypercholesterolemic and endothelium-denuded rats.