Introduction
Neonatal inhibition of the renin-angiotensin system in the rat results in long term abnormal renal morphology and function including interstitial inflammation and fibrosis. Renal hyaluronan (HA) has pathological implications in inflammatory diseases. The present study aimed at determining if renal cortical HA is correlated to the abnormal morphology and function observed in adult rats neonatally treated with the ACE-inhibitor enalapril (ENA).
Methods
Rats were treated daily between 3 and 13 days of age with ENA (10 mg/kg) or vehicle. Histology and analysis of HA content in kidneys were performed at day 21 or after 23 weeks of age (adults). At 13 weeks of age animals were put individually in metabolic cages and deprived of water for 24 hours to evaluate submaximal urinary concentrating ability.
Results
In control rats, the cortical HA content was very low (5-7 µg/g dry weight) at 21 days of age and during adulthood (23 weeks). In rats treated daily with ENA the cortical HA level was more than 15-fold higher (90-94 µg/g dw) than in control rats 21 days after birth and during adulthood. Cortical accumulation of infiltrating cells was evident at day 21 and during adulthood. At 13 weeks of age ENA treated animals showed markedly reduced ability (-53%) to concentrate urine during 24h thirst provocation. At 23 weeks papillary atrophy, dilatation of the tubules and cellular infiltration of the cortical tissue was evident. Histochemical staining confirmed the HA quantification assay and revealed a patchy interstitial staining for HA located to the same regions as the infiltrating cells.
Conclusions
In conclusion, neonatal treatment with ENA results in long term renal morphological and functional abnormalities. Cortical HA is severely elevated and coexists with infiltrating cells. Besides the known effects of angiotensin II in development, the accumulation of HA may explain at least the abnormal cortical findings in ENA treated animals due to the proinflammatory and water binding properties of HA.
References