DOWN-REGULATION OF THE INTRARENAL RENIN-ANGIOTENSIN SYSTEM IN THE AGING RAT

Progressive deterioration of renal function occurs during normal aging . Previous studies on the aging kidney have demonstrated glomerular he modynamic changes, specifically, glomerular capillary hypertension, as maladaptations that lead to proteinuria and glomerular sclerosis over time. Aging rats treated with angiotensin-converting enzyme inhibitio n have relatively less proteinuria and sclerosis, suggesting that age- related changes in renal function may be associated with alterations i n the intrarenal renin-angiotensin system, which thus may play a major role in the pathogenesis of these maladaptations. To investigate this possibility, renal and systemic renin-angiotensin systems were examin ed at an early phase of the aging process (3 months) and at a later ph ase (12 months) in male Sprague-Dawley rats. Although plasma renin and serum angiotensin-converting enzyme concentrations did not differ sig nificantly, the intrarenal system showed down-regulation of renin mRNA and angiotensin-converting enzyme levels with aging, whereas angioten sinogen levels remained stable. The decrease in renin mRNA appeared to precede the fall in plasma renin concentration in the aging process. Additional studies in 15-month-old rats confirmed that, by this time, both basal and stimulated renal renin release rates were impaired in o lder rats. Thus, both decreased renin synthesis and impaired renin rel ease underlie the fall in plasma renin with normal aging. This decreas e may act to lower intrarenal baseline levels of angiotensin II, an ad aptation of likely importance in the modulation of intrarenal vascular tone and tubular function in the aging kidney.