FUNCTIONAL VERSUS STRUCTURAL-CHANGES IN THE PATHOPHYSIOLOGY OF ACUTE ISCHEMIC RENAL-FAILURE IN AGING RATS

The aim of the study was to gain further insight into the greater susc eptibility to acute ischemic renal failure (ARF, 30 min of renal arter ies clamping) of old rats (O, 18 months) as against young rats (Y, 3 m onths). All the rats ate a hypoproteic diet (14% of casein) to avoid a ge-related glomerulosclerosis in O. Basal renal dynamics was similar i n O and Y (Groups CON). One day after ARF, the decrease in GFR was mor e severe in O than in Y (-82% and -57% vs. respective CON, P < 0.05), due to a greater rise of RVR in O (+258%) than in Y (+104%). The histo logic renal damage after ischemia was comparable in the two groups wit h ARF. Five days after ARF, the recovery of renal function was charact erized by a slower rise of GFR in O than in Y. In two further groups, two different scavengers of oxygen-free radicals, dimethylthiourea (DM TU) and superoxide dismutase (SOD), were administered at the time of a rterial occlusion. DMTU had protective effects in Y but not in O (Delt a GFR was -28% and -72%, respectively); in contrast, SOD was more effe ctive in O (Delta GFR = -58%) than in Y rats (Delta GFR = -40%). To te st the hypothesis that such a difference was related to the capacity o f SOD to increase the levels of nitric oxide (NO), four more groups of Y and O rats were pretreated with L-arginine (ARG), precursor of NO, in tap water (1.5%). No difference in renal dynamics was detected in b asal conditions. However, after ARF, while in Y no change was observed , in O rats, ARG led to a lesser decrease of GFR (-57% vs. CON) like i n SOD-O. Concomitant administration of a NO synthase inhibitor, N-nitr o-L-arginine-methyl-ester (50 mg/liter in tap water), prevented the be neficial effects of ARG. In conclusion, this study suggests that: (a) ischemic ARF is worse in O than Y rats even in absence of age-related glomerulosclerosis; (b) the greater renal impairment following ARF in O rats is likely related to reduced NO levels.