This study will focus upon the physiological receptors which mediate the effects of angiotensin in the body. Radioligand binding studies will be used to pharmacologically characterize and quantitate angiotensin receptors in the brain, adrenal and vascular smooth muscle of the rat and dog under conditions of experimental hypertension and altered dietary sodium intake. The initial phase of this study will be concerned with establishment of the optimal conditions for measuring angiotensin receptors in vitro. Of greatest concern will be: 1) establishment of conditions which prevent decomposition of the radiolabelled angiotensin; 2) comparison of the binding parameters of 125I labelled and 3H labelled angiotensin II; 3) determination of the tissue preparation and incubation medium components which - a) favor the highest angiotensin receptor binding affinity; b) the highest receptor concentration; and c) the highest ratio of specific to nonspecific tissue binding of angiotensin. The second phase of this project will assess the ability of a number of angiotensin analogs synthesized by Dr. Mahesh Khosla here at the Cleveland Clinic) to compete with radiolabelled angiotensin binding to angiotensin recerptors. The stability of angiotensin analogs to hydrolysis by tissue peptidases will also be assessed by radioreceptor assay following their incubation with tissue homogenates. The specific aim of this study will be to assess pharmacological differences between the angiotensin receptors in different tissues, utilizing analogs of angiotensin currently being developed under HL-6835 which preferentially interact with angiotensin receptors specific to an individual tissue and are resistant to degradation by proteolytic enzyme. The third phase of this project will assess angiotensin receptor alterations in canine experimental hypertension and altered dietary sodium intake, conditions known to have substantial impact on the renin-angiotensin system. Changes in angiotensin receptor densities, affinities or pharmacological profiles will be assessed to determine the importance of their role in the production or maintenance of hypertension and adaptation to changes in dietary sodium intake.