Activity and responsiveness of the renin-angiotensin system in the aging rat

The systemic renin-angiotensin system (RAS) is suppressed in normal aging, but the activity of the tissue RAS is not well defined. We examined the sys temic and intrarenal RAS status of aging normal rats and responses to suppr ession and stimulation of the production of endogenous ANG II. Studies were performed in young (3 mo) and early aging (15 mo) male Sprague-Dawley rats . Angiotensin-converting enzyme inhibitors modestly decreased mean arterial pressure (MAP) in young (3 mo) and early aging (15 mo) rats and limited pr oteinuria in the older rats. There were no significant age-related effects on renal function or on endogenous RAS activity. Intravenous infusion of th e precursor ANG I led to comparable increases in MAP in younger and older r ats. In contrast, the renal effects (reduction in glomerular filtration and plasma flow rates) were exaggerated in the older animals. Intrarenal arter ial ANG I did not affect MAP in any group. In young rats, there were no sig nificant hemodynamic effects in either the ipsilateral (infused) or the con tralateral (noninfused) kidney. In the older rats, both kidneys had a signi ficant fall in renal renal plasma flow rate (RPF) with left renal arterial infusion of ANG I. Accordingly, these studies early in the course of aging found only subtle changes in the activity, responsiveness, and metabolism o f the RAS. Thus early aging is associated with a modest but important incre ase in sensitivity to RAS stimulation.