Ontogeny of endothelin receptors in the brain, heart, and kidneys of neonatal rats

Background: Endothelin (ET) plays an important role in many physiological functions. It has been demonstrated that endogenous ET-1 concentration in the central nervous system (CNS) changes with age; however the ontogeny of ETA and ETB receptors in the brain, heart, and kidneys during postnatal development has not been studied. Methods: Brains, hearts and kidneys of rats at postnatal days 1, 7, 14 and 28 were evaluated for the expression of ETA and ETB receptors via Western blot. ETB receptors within the developing brain were further accessed via immunofluorescence. Results: The mean organ and body weights increased proportionally with advancing age demonstrating normal growth. The expression of ETA receptors in the brain, heart, and kidneys and ETB receptor expression in the heart and kidneys was similar in these rats at postnatal ages 1, 7, 14 and 28 days. However, brain ETB receptor expression significantly (P < 0.001) decreased by 72% on day 28 compared to the levels on postnatal day 1. Upon immunofluorescent analysis, the intensity of ETB staining in the cerebral cortex and subventricular zones of the developing rat brain decreased significantly from day 1 to day 7 (P < 0.001) and from day 7 to day 14 (P < 0.0001). There was no further decrease in ETB intensity noted in the cerebral cortex and subventricular zones between day 14 and day 28 of postnatal age. The intensity of ETB receptor staining within the cerebrovasculature, on the other hand, increased significantly (P < 0.05) from days 1 and 7 to day 14. Conclusions: These results demonstrate that expression of ETA receptors does not change with postnatal development. On the other hand ETB receptors in the cerebral cortex and subventricular zones of the brain decrease with age, while ETB receptors in the cerebrovasculature increase with age, implicating ETB receptor involvement in the structural maturity and development of the CNS.