Several recent studies, including one from our laboratory, have suggested that intrarenal levels of angiotensin II are an important determinant of the progression of renal failure in a variety of chronic conditions. Antidiuretic hormone (ADH) has also been implicated recently in the decline of function in chronic renal failure and in the development of renal hypertrophy. This study will evaluate the hypothesis that the vasoactive hormones angiotensin II and ADH mediate the age-related changes in renal function observed in humans and experimental animals. Experiments will be carried out to determine whether increased levels of intrarenal angiotensin II mediate age-related decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) and whether physiological levels of ADH influence age-related decreases in renal function and the development of senile hypertrophy. The mechanisms responsible for the decrease in urinary concentrating ability with age will also be explored to determine whether this is secondary to the decline in GFR or results from a primary alteration in the renal concentrating process, e.g. reduced NaCl reabsorption in the loop of Henle and/or reduced tubular responsiveness to ADH. The studies will be carried out in adult, old and senescent rats, either normal or homozygous for the diabetes insipidus trait (DI rats). Use of this animal model will allow direct evaluation of the role of ADH in age-related changes in renal function. The research questions posed here have not been addressed previously and have important biomedical relevance. Should angiotensin II and ADH be found to mediate the decline in renal function with age, a variety of potential therapeutic measures are presently available whose efficacy in ameliorating this decline could be evaluated promptly. Similarly, identifying the physiological mechanisms underlying reduced concentrating ability will also suggest appropriate therapeutic interventions. Finally, this project offers an attractive opportunity to involve students in a research project with important health relevance and expose them to a variety of classic research techniques.
Showing the most recent 10 out of 174 publications
