title: Angiotensin-converting enzyme inhibition aggravates renal interstitial injury resulting from partial unilateral ureteral obstruction in the neonatal rat.
abstract: Congenital urinary tract obstruction is the most important cause of renal insufficiency in infants and children, and angiotensin-converting enzyme (ACE) inhibitors attenuate the progression of renal disease in adults. ACE inhibitors are increasingly utilized in children with progressive renal disease. Because angiotensin is necessary for normal renal development, we examined the effects of ACE inhibition both during and immediately following the period of postnatal nephrogenesis in the neonatal rat subjected to sham operation or partial unilateral ureteral obstruction (UUO) under general anesthesia within the first 48 h of life. Rats in group I received enalapril 30 mg/kg body wt (or vehicle) daily for the first 10 days, while in group II, the 10 days of treatment began 10 days after surgery. Kidneys were harvested at day 21 and analyzed for apoptosis (TUNEL), interstitial macrophages (ED-1 immunohistochemistry), myofibroblasts (alpha-smooth muscle actin), and collagen (Sirius red). Partial UUO delayed glomerular maturation and increased ipsilateral renal macrophage infiltration, alpha-smooth muscle actin and Sirius red staining. In group I, enalapril increased myofibroblast accumulation in sham-operated kidneys, but not in obstructed kidneys. In contrast, in group II, enalapril further increased macrophage, myofibroblast, and collagen accumulation following partial UUO. The relative abundance of components of the kallikrein-kinin system, measured by Western blot, was not altered by partial UUO in the 14- and 28-day-old rat. Thus, in contrast to its salutary effects at later ages, ACE inhibition can worsen injury to the partially obstructed kidney during renal maturation even after the completion of nephrogenesis.
authors.affiliation: Department of Pediatrics, University of Virginia, Box 800386, Charlottesville, VA 22908, USA.
authors.forename: Christina O
authors.initials: CO
authors.lastname: Chen
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Park
authors.forename: Michael S
authors.initials: MS
authors.lastname: Forbes
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Thornhill
authors.forename: Susan C
authors.initials: SC
authors.lastname: Kiley
authors.forename: Kee Hwan
authors.initials: KH
authors.lastname: Yoo
authors.forename: Robert L
authors.initials: RL
authors.lastname: Chevalier
mesh_terms: D000199:Actins / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D000075202:Contraindications; D004656:Enalapril / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007679:Kidney Medulla / Q000378:metabolism / Q000473:pathology; D007682:Kidney Pelvis / Q000187:drug effects / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007704:Kininogens / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2 / Q000378:metabolism; D020840:Tissue Kallikreins / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications*
chemical_list: D000199:Actins; D000806:Angiotensin-Converting Enzyme Inhibitors; D003094:Collagen; D004656:Enalapril; D007704:Kininogens; D043782:Receptor, Bradykinin B2; D020840:Tissue Kallikreins; C498862:Acta2 protein, rat