The overall objective of this proposal is to develop a quantitative systems analysis of the long-term importance of the renin-angiotensin system (RAS), kallikrenin-kinin system, renal prostaglandins (PG's), and adrenocortical hormones in regulating renal hemodynamics, electrolyte excretion, body fluid volumes, and arterial pressure. Since there is very little quantitative information available on the long-term effects of these hormones on renal function in intact conscious animals, all of the proposed studies will be conducted in intact conscious dogs. The effectiveness of these hormonal systems in regulating renal function after various perturbations such as changes in salt and water intake or changes in renal artery pressure will be quantitated in normal intact dogs (closed-loop feedback conditions) and in dogs where one or more of the hormonal feedbacks have been interrupted (open-loop feedback conditions) by surgical techniques (i.e., adrenalectomy) and chemical methods (i.e., infusion of angiotensin converting enzyme inhibitors, PG synthetase inhibitors, and by chronic iv infusion of angiotensin II, PG's, glucocorticoids, and mineralocorticoids). Changes in renal function after these perturbations will be quantitated with techniques recently developed in our laboratory which allow us to accurately estimate glomerular filtration rate and effective renal plasma flow day after day for long periods of time without disturbing the animal and without repeated bladder catheterizations. Also techniques developed for continuous recording of blood pressure 24 hours a day, continuous intravenous infusions, and for measurement of other indices of renal and endocrine function will be utilized in these studies. Since essentially all of the experiments will be conducted over a period of several days or weeks in conscious animals, we believe that these studies will provide us with reliable quantitative data which will be invaluable in developing a systems analysis of the importance of these hormonal systems in regulating renal function as well as body fluid volumes and arterial pressure.
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