Renal cortical accumulation of hyaluronan in adult rats exposed neonatally to angiotensin‐converting enzyme inhibition

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Abstract
Neonatal inhibition of the renin–angiotensin system [angiotensin‐converting enzyme (ACE) inhibition] in the rat results in long‐term abnormal renal morphology and function, including interstitial inflammation and fibrosis. Hyaluronan (hyaluronic acid, HA) has pathological implications in inflammatory diseases and renal ischaemia‐reperfusion injury. The present study aimed at determining if renal cortical HA in the adult rat is correlated to the abnormal morphology and function in rats treated neonatally with the ACE inhibitor enalapril. In adult control rats (23 weeks old), the cortical HA content was very low [about 5 μg 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 15 times that in control rats already at 21 days after birth, and it persisted at this level during adulthood (at 23 weeks). At 13 weeks the enalapril‐treated animals showed markedly reduced ability (–53%) to concentrate urine during 24‐h thirst provocation. At 21 days as well as at 23 weeks the enalapril‐treated kidneys displayed morphological changes, such as papillary atrophy, dilation of the tubules and cellular infiltration 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 with the ACE inhibitor enalapril results in renal morphological and functional 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 kidneys may be involved in the genesis of at least the cortical abnormalities in enalapril‐treated animals because of the proinflammatory effects and water‐binding properties of HA.