PREVENTION OF CARDIOVASCULAR AND RENAL PATHOLOGY OF AGING BY THE ADVANCED GLYCATION INHIBITOR AMINOGUANIDINE

Human aging is impacted severely by cardiovascular disease and signifi cantly but less overtly by renal dysfunction. Advanced glycation endpr oducts (AGEs) have been linked to tissue damage in diabetes and aging, and the AGE inhibitor aminoguanidine (AG) has been shown to inhibit r enal and vascular pathology in diabetic animals. In the present study, the effects of AG on aging-related renal and vascular changes and AGE accumulation were studied in nondiabetic female Sprague-Dawley (S-D) and Fischer 344 (F344) rats treated with AG (0.1% in drinking water) f or 18 mo. Significant increases in the AGE content in aged cardiac (P < 0.05), aortic (P < 0.005), and renal (P < 0.05) tissues were prevent ed by AG treatment (P < 0.05 for each tissue). A marked age-linked vas odilatory impairment in response to acetylcholine and nitroglycerine w as prevented by AG treatment (P < 0.005), as was an age-related cardia c hypertrophy evident in both strains (P < 0.05). While creatinine cle arance was unaffected by aging in these studies, the AGE/creatinine cl earance ratio declined 3-fold in old rats vs. young rats (S-D, P < 0.0 5; F344, P < 0.01), while it declined significantly less in AG-treated old fats (P < 0.05). In S-D but not in F344 rats, a significant (P < 0.05) age-linked 24% nephron loss was completely prevented by AG treat ment, and glomerular sclerosis was markedly suppressed (P < 0.01). Age -related albuminuria and proteinuria were markedly inhibited by AG in both strains (S-D, P < 0.01; F344, P < 0.01). These data suggest that early interference with AGE accumulation by AG treatment mag impart si gnificant protection against the progressive cardiovascular and renal decline afflicting the last decades of life.