Renal interstitial sclerosis in aging: effects of enalapril and nifedipine.
The effects of nifedipine and enalapril on age-associated renal interstitial fibrosis were investigated in 60 CF1 female mice. Mice received 20 mg enalapril (ENAL) per L (N = 20), or 40 mg nifedipine (NIF) per L (N = 20) in their drinking water. Control (CONT) mice received tap water ad libitum. The percentages of both interstitial peritubular sclerosis (IPS) in cortex and interstitial medullary sclerosis (IMS) were determined. Kidney tissue was studied using immunological techniques and optical (OM) and electron microscopy (EM) to analyze the expression of renin. alpha-SM-actin and vimentine expression were also evaluated. The results showed that blood pressure levels in ENAL or NIF animals were not different from those of CONT. Renin expression was observed in arcuate vessels (AV) in ENAL animals, whereas no renin staining in AV was found in either NIF or CONT animals. Renin immunoreactivity in the juxtaglomerular apparatus was more intense in ENAL mice, as compared with NIF or CONT animals. Laboratory testing showed the following values: proteinuria (mg/mL): CONT 6.1 +/- 0.6, NIF 11.2 +/- 2.3, and ENAL 1.0 +/- 0.6 (P < 0.05); creatinine: CONT 1.37 +/- 0.24, NIF 0.87 +/- 0.16, and ENAL 0.63 +/- 0.1 (P < 0.01). The percentages of interstitial sclerosis were: %IPS: CONT 18.12 +/- 1.1, NIF 17.40 +/- 0.9, and ENAL 3.42 +/- 1.3 (P < 0.01); %IMS: CONT 23.41 +/- 1.5, NIF 21.80 +/- 1.9, and ENAL 6.12 +/- 1.2 (P < 0.01). Percentages of alpha-SM-actin expression were: CONT 13.10 +/- 1.9, NIF 13.80 +/- 0.2, and ENAL 1.00 +/- 0.1 (P < 0.01). Vimentine staining showed no differences among the groups. It was concluded that enalapril reduces the peritubular and medullar interstitial fibrosis, whereas nifedipine has no effect.
Inserra
F
F
Institute of Nephrology, Jewish Hospital, Buenos Aires, Argentina.
Romano
L A
LA
de Cavanagh
E M
EM
Ercole
L
L
Ferder
L F
LF
Gomez
R A
RA
D000199:Actins / Q000378:metabolism; D000375:Aging / Q000473:pathology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000187:drug effects; D012598:Sclerosis; D014746:Vimentin / Q000378:metabolism
D000199:Actins; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D002121:Calcium Channel Blockers; D014746:Vimentin; D004656:Enalapril; D009543:Nifedipine