Early lesions of cerebral atherosclerosis from induced hypertension in Watanabe heritable hyperlipidemic rabbits.

Watanabe heritable hyperlipidemic (WHHL) rabbits are well known to develop severe atherosclerotic lesions in extracranial arteries but not in cerebral arteries. In the present work we produced and investigated atherosclerotic lesions in cerebral arteries of WHHL rabbits by inducing hypertension. Hypertension was induced by right nephrectomy and surgically induced stenosis of the left renal artery. Six months after surgery the rabbits were killed for morphologic, immunohistochemical and transmission electron microscopic studies of extracranial and cerebral atherosclerosis. A significant rise in systolic blood pressure was evident 3 months after surgery in the hypertensive group (p < .001). Atherosclerotic lesions had developed areas near the vertebral-basilar arterial confluence and the circle of Willis in the hypertensive Watanabe rabbits by 6 months after surgery (p < .001). Atherosclerotic lesions in cerebral arteries remained less severe than in the aorta and coronary arteries, and showed qualitative morphologic differences. This is the first report of production by hypertension of experimental cerebral atherosclerosis in the WHHL rabbits, indicating that hypertension as well as hyperlipidemia was required for development of lesions in cerebral arteries. This model should be useful for studying development of cerebral atherosclerosis and may contribute to improved prevention and treatment of the human disease.