Changes of Renal AT₁/AT₂ Receptors and Structures in Ovine Fetuses following Exposure to Long-Term Hypoxia

Abstract

Background/Aims: The present study tested the hypothesis that chronic hypoxia adversely affects renal development in the ovine fetus. Methods: Kidneys were collected from near-term fetuses of pregnant ewes maintained at sea level or high altitude (3,801 m, PaO₂: approx. 60 mm Hg) for 110 days (n = 6 for each group). Results: Long-term high altitude hypoxia reduced the fetal kidney/body weight ratio. Histological analysis showed a significant enlargement in the Bowman’s space and swelling of tubule epithelial cells in the kidney of the hypoxic fetus. The histological alterations were limited to the cortical, but not medullary, zone. These alterations were associated with an increase in serum creatinine and a decrease in the BUN-to-creatinine ratio in hypoxic fetuses. Angiotensin II receptors (AT₁R and AT₂R) were detected in the glomerular and tubular regions of the kidney. Chronic hypoxia caused a significant increase in AT₁R and a decrease in AT₂R protein and mRNA abundance, resulting in a large increase in the AT₁R/AT₂R ratio in the fetal kidney. Conclusion: The results demonstrate an adverse effect of chronic hypoxia on renal AT₁R and AT₂R expression and functions in the fetus, suggesting a possible role of fetal hypoxia in the programming of renal diseases in fetal origins.

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