Glomerular number and size following chronic angiotensin II blockade in the postnatal rat.
Chronic angiotensin-converting enzyme (ACE) inhibition with enalapril or angiotensin II (Ang II) receptor antagonism with either losartan (specific for Ang II type-1 receptor, AT1) or PD 123319 (specific for the Ang II type-2 receptor, AT2) were effected between postnatal days 3 and 21 in the rat. Following quantitative analysis of the kidneys using recently developed unbiased stereological techniques we found that none of the treatments resulted in changes in glomerular number or size. This implies that inhibition of Ang II activity had no effect on postnatal nephron induction or glomerular development. However, following both chronic ACE inhibition and AT1 antagonism, abnormalities of tubules and their associated vessels were evident throughout the kidney and were accompanied by an increased proportion of interstitium. The structural abnormalities were most prominent in the outer medulla and were consistent with interruption of descent of the loops of Henle and vasa rectae. In contrast, no renal morphological abnormalities were observed following chronic AT2 antagonism.
McCausland
J E
JE
Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Vic., Australia.
Bertram
J F
JF
Ryan
G B
GB
Alcorn
D
D
D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D001713:Biphenyl Compounds / Q000633:toxicity; D004656:Enalapril / Q000633:toxicity; D005260:Female; D007093:Imidazoles / Q000633:toxicity; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000254:growth & development*; D007684:Kidney Tubules / Q000002:abnormalities / Q000187:drug effects / Q000254:growth & development; D019808:Losartan; D008855:Microscopy, Electron, Scanning; D011247:Pregnancy; D011725:Pyridines / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles / Q000633:toxicity
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D004656:Enalapril; D019808:Losartan