Acute studies in renal hypertensive rats indicate that functional and structural changes occur that contribute to the increase in peripheral resistance. The studies suggest that an early increase in vasoconstriction is superseded by structural alterations such as rarefaction of microvessels, reduction in arteriolar size, and increases in arteriolar wall thickness. Chronic studies are needed to document these changes on a daily basis during the development of hypertension. Vasomotion is an important contributor to vascular resistance and blood flow regulation which is studied best in conscious animals. It is the purpose of this study to examine and document all of these mechanisms in the conscious renal hypertensive rabbit using the ear chambter preparation. Measurements will be made of microvessel diameters and vasomotion by image splitting closed circuit television microscopy, red cell velocity by the dualslit photometric technique, capillary hematocrit by strobe-flash television microscopy, and microvessel density by in vivo quantitative stereology. Microvascular responses will be studied following the initiation of hypertension in the 1-kidney and 2-kidney-1-clip models until a new steady state is reached, approximately 2-6 months. Blood pressure measurements and blood samples for plasma renin activity will be obtained from a chronic catheter in the abdominal aorta. After these measurements of baseline data, experiments will be performed to study the mechanisms leading to the changes, such as the influence of the sympathetic nerves, the renin-angiotensin system, and myogenic responses to increased and decreased intralumenal pressure. In other studies the renal artery will be unclipped before and after hypertension becomes irreversible to study the regression of the structural changes and to see if they play any role in the irreversibility of long term renal hypertension. These studies in the conscious rabbit will provide the information to assess morphological and functional changes in hypertension and hypotension, their time scale, cause, and functional significance concerning long term regulation of blood flow.
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