title: Long-term reduction of renal interstitial hydrostatic pressure after neonatal renin-angiotensin system inhibition in the rat.
abstract: BACKGROUND
  Neonatal inhibition of the renin angiotensin system (RAS) causes a decreased urinary concentrating ability, papillary atrophy, and tubulointerstitial inflammation long term. As a consequence of these morphological changes, we surmised that renal blood flow and renal interstitial hydrostatic pressure (RIHP) may be altered during and shortly after cessation of neonatal angiotensin-converting enzyme (ACE) inhibition, and that tentative changes of these variables would persist long after treatment withdrawal.
  
  
  METHODS
  Rats were given daily intraperitoneal injections of the ACE inhibitor, enalapril (10 mg/kg) or saline from days 3 to 23 postpartum, and the relationship between renal perfusion pressure (PP) and RIHP was investigated in 6- and 13-week-old anaesthetized rats.
  
  
  RESULTS
  Neonatal ACE inhibition did not affect baseline RIHP short term, whereas RIHP was reduced at 13 weeks of age versus controls (11.6+/-1.6 vs 18.5+/-1.0 mmHg, P<0.05). Changes in RIHP correlated positively to changes in renal PP, independent of treatment and age (slope averaged 0.11+/-0.03). Ongoing ACE inhibition until 6 weeks of age neither affected baseline RIHP nor altered the reactivity to changes in perfusion pressure. Mild renal histopathological abnormalities were present already 3 weeks after cessation of treatment and were aggravated significantly in the 13-week-old rats, showing a complete loss of the papillary parenchyma.
  
  
  CONCLUSIONS
  The reduced baseline RIHP in adult rats seemed to constitute a functional correlate to the major papillary atrophy. However, RIHP responses to changes in renal perfusion pressure was maintained, possibly indicating a compensatory effect of the remaining vasa recta and/or peritubular capillary network. Taken together, lack of neonatal angiotensin II type-1 (AT1) receptor stimulation induces not only irreversible abnormalities of the renal architecture, but causes alteration of intrarenal haemodynamics, such as a reduced RIHP, which may have implications for the regulation of pressure-natriuresis.
authors.affiliation: Department of Physiology, Institute of Physiology and Pharmacology, Göteborg University, Sweden.
authors.forename: A B
authors.initials: AB
authors.lastname: Nilsson
authors.forename: M A
authors.initials: MA
authors.lastname: Adams
authors.forename: S J
authors.initials: SJ
authors.lastname: Matthews
authors.forename: G S
authors.initials: GS
authors.lastname: Guron
authors.forename: B
authors.initials: B
authors.lastname: Sundelin
authors.forename: P
authors.initials: P
authors.lastname: Friberg
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006874:Hydrostatic Pressure; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D010477:Perfusion; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril