Background: This study aimed to examine whether and how postnatal high-fat diet had additional impact on promoting vascular dysfunction in the offspring exposed to prenatal hypoxia.
Methods and results: Pregnant Sprague-Dawley rats were randomly assigned to hypoxia (10.5% oxygen) or normoxia (21% O2 ) groups from gestation days 5-21. A subset of male offspring was placed on a high-fat diet (HF, 45% fat) from 4-16 weeks of age. Prenatal hypoxia induced a decrease in birth weight. In offspring-fed HF diet, prenatal hypoxia was associated with increased fasting plasma triglyceride, total cholesterol, free fatty acids, and low-density lipoprotein-cholesterol. Compared with the other three groups, prenatal hypoxic offspring with high-fat diet showed a significant increase in blood pressure, phenylephrine-mediated vasoconstrictions, L-type voltage-gated Ca2+ (Cav1.2) channel currents, and elevated mRNA and protein expression of Cav1.2 α1 subunit in mesenteric arteries or myocytes. The large-conductance Ca2+-activated K+ (BK) channels currents and the BK channel units (β1, not α-subunits) were significantly increased in mesenteric arteries or myocytes in HF offspring independent of prenatal hypoxia factor.
Conclusion: The results demonstrated that prenatal hypoxia followed by postnatal HF caused vascular dysfunction through ion channel remodelling in myocytes.
Keywords: L-type calcium channels; high fat; ion channels; prenatal; voltage-gated potassium channels.
© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.