Renal cortical accumulation of hyaluronan in adult rats exposed neonatallyto angiotensin-converting enzyme inhibition

Neonatal inhibition of the renin-angiotensin system [angiotensin-converting enzyme (ACE) inhibition] in the rat results in long-term abnormal renal mo rphology and function, including interstitial inflammation and fibrosis. Hy aluronan (hyaluronic acid, HA) has pathological implications in inflammator y diseases and renal ischaemia-reperfusion injury. The present study aimed at determining if renal cortical HA in the adult rat is correlated to the a bnormal morphology and function in rats treated neonatally with the ACE inh ibitor enalapril. ln adult control rats (23 weeks old), the cortical HA con tent was very low [about 5 mug g(-1) dry weight (d.w.)] and about 1% of the papillary HA content. In rats treated neonatally with enalapril (days 3-13 ), the cortical HA level was IS times that in control rats already at 21 da ys after birth, and it persisted at this level during adulthood (at 23 week s). At 13 weeks the enalapril-treated animals showed markedly reduced abili ty (-53%) to concentrate urine during 24-h thirst provocation, At 21 days a s well as at 23 weeks the enalapril-treated kidneys displayed morphological changes, such as papillary atrophy, dilation of the tubules and cellular i nfiltration of the cortical tissue. Histochemical staining confirmed the HA quantification assay and revealed a patchy staining for HA located In the same regions as the infiltrating cells. In conclusion, neonatal treatment w ith the ACE inhibitor enalapril results in renal morphological and function al abnormalities during adulthood. Cortical HA levels are already seriously elevated at day 21 and coexist with infiltrating cells. Besides the known effects of angiotensin II in development, the accumulation of HA in these k idneys may be involved in the genesis of at least the cortical abnormalitie s in enalapril-treated animals because of the proinflammatory effects and w ater-binding properties of HA.