Angiotensin converting enzyme inhibition in the postnatal rat results in decreased cell proliferation in the renal outer medulla.
1. Chronic angiotensin converting enzyme (ACE) inhibition or AT1 antagonism during postnatal development in the rat has been shown to cause renal tubular and vascular damage, particularly in the outer medulla. 2. The effects of ACE inhibition were investigated at a stage of development before the renal outer medulla is fully established. 3. Sprague-Dawley rat pups were given daily i.p. injections of either enalapril or saline from days 3-10. At day 11, kidneys were perfusion-fixed for either electron microscopy or immunocytochemistry. Sections were incubated in proliferating cell nuclear antigen (PCNA) antisera and the avidin-biotin immunoperoxidase method was used to detect an immunoreactive product, indicative of proliferating cells. 4. Following enalapril treatment, the normal structural arrangement of the outer medulla was disrupted compared with controls. Cell proliferation (PCNA-positive cells) in the medullary rays was reduced in enalapril-treated kidneys compared with control kidneys. 5. Thus, angiotensin II appears to be essential for normal tubular and vascular growth in postnatal renal development in the rat.
McCausland
J E
JE
Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria, Australia.
Ryan
G B
GB
Alcorn
D
D
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D015773:Enalaprilat / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007672:Kidney Cortex / Q000187:drug effects / Q000254:growth & development; D007679:Kidney Medulla / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D015773:Enalaprilat