Prenatal hypoxia plus postnatal high‐fat diet exacerbated vascular dysfunction via up‐regulated vascular Cav1.2 channels in offspring rats

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% O(2)) 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.