Long-term reduction of renal interstitial hydrostatic pressure after neonatal renin-angiotensin system inhibition in the rat.

Abstract

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. 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. 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. 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.