Glomerular adaptations with normal aging and with long-term converting enzyme inhibition in rats.
Normal aging is accompanied by renal functional and structural deterioration. To examine the hemodynamic and growth-related mechanisms of age-associated nephron loss, as well as the potential beneficial effects of antihypertensive therapy, studies were performed in normal aging Munich-Wistar rats, and in rats receiving long-term antihypertensive therapy with the converting enzyme inhibitor (CEI) enalapril. In protocol 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 pressure but increased glomerular capillary pressure due to a reduction in afferent arteriolar resistance. Glomerular size increased proportionately to changes in body weight, while kidney weight increased to a lesser degree. Albuminuria rose significantly after 10 mo of age and was accompanied by development of modest, but significant, glomerular sclerosis. CEI therapy from the age of 3 mo lowered systemic and glomerular capillary pressures, did not affect glomerular size, and significantly 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 development of sclerosis were significantly attenuated, although not entirely prevented. These findings suggest that hemodynamic maladaptations may contribute to age-related loss of renal function in the rat and that antihypertensive therapy may serve to delay this process.
Anderson
S
S
Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Rennke
H G
HG
Zatz
R
R
D000222:Adaptation, Physiological; D000375:Aging / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D004656:Enalapril / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril