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

Background. Neonatal inhibition of the renin-angiotensin system (RAS) cause s a decreased urinary concentrating ability, papillary atrophy, and tubulo- interstitial inflammation long term. As a consequence of these morphologica l changes, we surmised that renal blood flow and renal interstitial hydrost atic pressure (RIHP) may be altered during and shortly after cessation of n eonatal 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 inhibi tor, enalapril (10 mg/kg) or saline from days 3 to 23 postpartum, and the r elationship 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, w hereas RIHP was reduced at 13 weeks of age versus controls (11.6+/-1.6 vs 1 8.5+/-1.0 mmHg, P<0.05). Changes in RIHP correlated positively to changes i n 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 his topathological abnormalities were present already 3 weeks after cessation o f treatment and were aggravated significantly in the 13-week-old rats, show ing a complete loss of the papillary parenchyma. Conclusion. The reduced baseline RIHP in adult rats seemed to constitute a functional correlate to the major papillary atrophy. However, RIHP response s to changes in renal perfusion pressure was maintained, possibly indicatin g a compensatory effect of the remaining vasa recta and/or peritubular capi llary network. Taken together, lack of neonatal angiotensin II type-1 (AT(1 )) receptor stimulation induces not only irreversible abnormalities of the renal architecture, but causes alteration of intrarenal haemodynamics, such asa reduced RIHP, which may have implications for the regulation of pressu re-natriuresis.