The major goal of the present study is to assess the role of hypertension on the development of atherosclerosis in two different arterial beds, the carotid artery and aorta, and to determine similarities or differences in the responses of these two beds to intervention with the calcium blocking agent, isradipine. The hypothesis to be tested is that carotid artery atherosclerosis in hypertensive animals develops at a significantly greater rate and is less subject to regression compared to aortic atherosclerosis. White Carneau pigeons, aged 6-12 months and of either sex, from genetically selected high (n=91) and low (n=91) blood pressure lines will be studied. The birds in each line will be divided into four groups and will be fed either an atherogenic or control diet. Blood pressure, body weight, plasma cholesterol, blood calcium and plasma lipoprotein concentrations will be measured initially, and at 3 and 10 months during the study. After 10 months, subgroups of pigeons will be examined to assess atherosclerosis. The remaining pigeons will be removed from the atherogenic diet and divided into three subgroups. During any atherosclerosis regression phase, a control diet with or without isradipine will be fed for an additional 10 months. The birds will be sacrificed and atherosclerosis evaluated by visual examination, total arterial cholesterol, calcium, collagen and elastin concentrations. Histologic sections will be examined to support the biochemical studies. The significance of the project lies in a better understanding of the role of hypertension in atherosclerosis development in aorta and carotid artery and the response of these two arterial beds to dietary intervention and the effect of the calcium channel blocker, isradipine.
