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 susceptibility to acute ischemic renal failure (ARF, 30 min of renal arteries clamping) of old rats (O, 18 months) as against young rats (Y, 3 months). All the rats ate a hypoproteic diet (14% of casein) to avoid age-related glomerulosclerosis in O. Basal renal dynamics was similar in O and Y (Groups CON). One day after ARF, the decrease in GFR was more 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 histologic renal damage after ischemia was comparable in the two groups with ARF. Five days after ARF, the recovery of renal function was characterized by a slower rise of GFR in O than in Y. In two further groups, two different scavengers of oxygen-free radicals, dimethylthiourea (DMTU) and superoxide dismutase (SOD), were administered at the time of arterial occlusion. DMTU had protective effects in Y but not in O (Delta GFR was -28% and -72%, respectively); in contrast, SOD was more effective in O (Delta GFR = -58%) than in Y rats (Delta GFR = -40%). To test the hypothesis that such a difference was related to the capacity of 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 basal 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 in SOD-O. Concomitant administration of a NO synthase inhibitor, N-nitro-L-arginine-methyl-ester (50 mg/liter in tap water), prevented the beneficial 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.