An abstract of the thesis of Michele McKee Thompson for the Master of Science in Biology presented June 27, 1997. Title: Age related changes in the activity and the responsiveness of the reninangiotensin system in the 15 month old rat. Progressive deterioration of renal function is one consequence of aging. Glomerular maladaptation is one aspect of this and includes increased glomerular capillary hypertension and a reduced ultrafiltration coefficient, which can lead to glomerular sclerosis and

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... roteinuria. In the aging rat, angiotensin converting enzyme inhibitors (CEI) lower proteinuria (UprotV) and decrease glomerular sclerosis (2, 18, 24, 45) . Accordingly, alterations in the circulating and renal renin-angiotensin system (RAS) are hypothesized to play a role in the pathogenesis of renal disease in the aging rat. Previous studies using rat models have demonstrated a lower responsiveness to converting enzyme inhibitor treatment in the older rat compared to the young and diabetic models (2, 12). However, these results are not found consistently (7). We treated young (3 month old) and older (15 month old) Sprague-Dawley rats with the converting enzyme inhibitor, enalapril, to investigate the responsiveness to this treatment, of the older rat compared to the young rat. Blood pressure, proteinuria, renal function, and blood and renal reninangiotensin component concentrations were compared in young and older male Sprague-Dawley rats treated for 4 weeks with two dose levels of enalapril. Young and older untreated controls received no enalapril treatment. All rats were normotensive at baseline and the older rats were proteinuric. Enalapril reduced systolic blood pressure in both age groups; however, this treatment failed to significantly reduce proteinuria in the older rats. Renal function decreased in the older rats. Enalapril treatment did not improve the renal function of either the young or the older rat. Mean arterial pressure was reduced, with enalapril treatment, in the young, but not the older rats. Biochemical RAS measurements were not altered with age. Plasma renin concentration, kidney angiotensin II (Ang II) and blood Ang II responded appropriately with the converting enzyme inhibitor enalapril, and showed no age-related responses to this treatment. We conclude that the 15 month old rat does not exhibit an age-related alteration in response to converting enzyme inhibition when compared to the young rat. At this transition age, the decline in renal function does not appear to be a consequence of an altered reninangiotensin system. 1997 ACKNOWLEDGMENTS The completion of this document involved the collective efforts of several generous and patient people. Stan Hillman gave me guidance and direction while demanding my best performance. In my three years at PSU, I have come to know the stability that is Stan Hillman. His devotion and support of his students makes him much more than a professor to all that have contact with him. He is a life teacher. Sharon Anderson generously gave me the support, flexibility and latitude to take on and complete this project. Her presence and standards influence my life and work. She has served as and will continue to be an ideal role model. I will always admire the grace with which she balances research, clinical medicine, administration and teaching. Deohdar are responsible for maintaining my spirit during this project. Their humor, kindness, support, advice and patience assisted me more than they can ever know. Terry, thank-you for the perspective and pragmatism. Tom, thank-you for guiding my path and focus, your advice always cleared the way. My mother and father, Laurie and Stephan Thompson, have provided the love and encouragement that has made this project possible.