GLOMERULAR ADAPTATIONS WITH NORMAL AGING AND WITH LONG-TERM CONVERTING-ENZYME INHIBITION IN RATS

Normal aging is accompanied by renal functional and structural deterio ration. To examine the hemodynamic and growth-related mechanisms of ag e-associated nephron loss, as well as the potential beneficial effects of antihypertensive therapy, studies were performed in normal aging M unich-Wistar rats, and in rats receiving long-term antihypertensive th erapy with the converting enzyme inhibitor (CEI) enalapril. In protoco l 1, rats were treated from the age of 3 mo. Compared with young rats, untreated old rats studied at 2.5 yr of age exhibited normal blood pr essure but increased glomerular capillary pressure due to a reduction in afferent arteriolar resistance. Glomerular size increased proportio nately to changes in body weight, while kidney weight increased to a l esser degree. Albuminuria rose significantly after 10 mo of age and wa s accompanied by development of modest, but significant, glomerular sc lerosis. CEI therapy from the age of 3 mo lowered systemic and glomeru lar capillary pressures, did not affect glomerular size, and significa ntly ameliorated development of albuminuria and structural injury. In protocol 2, untreated rats were compared with a treated group in which enalapril therapy was delayed until the age of 1 yr, when albuminuria was already rising. Subsequent increases in albuminuria and developme nt of sclerosis were significantly attenuated, although not entirely p revented. These findings suggest that hemodynamic maladaptations may c ontribute to age-related loss of renal function in the rat and that an tihypertensive therapy may serve to delay this process.