Decreased arterial responses in WHHL rabbits, an animal model of spontaneous hypercholesterolemia and atherosclerosis.

We examined changes in blood pressure and blood flow of the arteries of WHHL and Japanese white rabbits after intravenous bolus injections of acetylcholine (3.0 micrograms/kg), bradykinin (0.5 microgram/kg), and sodium nitroprusside (3.0 micrograms/kg) under a condition of anesthesia. These vasodilators lowered the blood pressure and increased the blood flow in WHHL and Japanese white rabbits. The changes in the hemodynamic parameters of WHHL rabbits after injection of sodium nitroprusside were similar to those of Japanese white rabbits. This suggests that the relaxation response of the tunica media was not diminished in WHHL rabbits. In contrast, the changes in the hemodynamic parameters of WHHL rabbits after injection of acetylcholine or bradykinin were significantly lower than those in Japanese white rabbits. In the histopathological and immunohistological examination, atherosclerotic lesions were observed in the ascending aortas of WHHL rabbits. In the surface of the atheromatous plaques, CD31-positive endothelial cells disappeared partly and the accumulation of RAM-11-positive macrophages was observed in these regions. In addition, plasma NO2- and NO3- levels of WHHL rabbits were significantly lower than those of Japanese white rabbits. These findings suggest that relaxation responses derived from arterial endothelial cells were probably depressed in WHHL rabbits due to dysfunction or denudation of the arterial endothelial cells.