Prenatal Hypoxia Induced Dysfunction in Cerebral Arteries of Offspring Rats

BACKGROUND Hypoxia during pregnancy could cause abnormal development and lead to increased risks of vascular diseases in adults. This study determined angiotensin II (AII)-mediated vascular dysfunction in offspring middle cerebral arteries (MCA). METHODS AND RESULTS Pregnant rats were subjected to hypoxia. Vascular tension in offspring MCA by AII with or without inhibitors, calcium channel activities, and endoplasmic reticulum calcium stores were tested. Whole-cell patch clamping was used to investigate voltage-dependent calcium channel currents. mRNA expression was tested using quantitative real-time polymerase chain reaction. AII-mediated MCA constriction was greater in male offspring exposed to prenatal hypoxia. AT1 and AT2 receptors were involved in the altered AII-mediated vasoconstriction. Prenatal hypoxia increased baseline activities of L-type calcium channel currents in MCA smooth muscle cells. However, calcium currents stimulated by AII were not significantly changed, whereas nifedipine inhibited AII-mediated vasoconstrictions in the MCA. Activities of IP3/ryanodine receptor-operated calcium channels, endoplasmic reticulum calcium stores, and sarcoendoplasmic reticulum membrane Ca2+-ATPase were increased. Prenatal hypoxia also caused dysfunction of vasodilatation via the endothelium NO synthase. The mRNA expressions of AT1A, AT1B, AT2R, Cav1.2α1C, Cav3.2α1H, and ryanodine receptor RyR2 were increased in the prenatal-hypoxia group. CONCLUSIONS Hypoxia in pregnancy could induce dysfunction in both contraction and dilation in the offspring MCA. AII-increased constriction in the prenatal-hypoxia group was not mainly dependent on the L-type and T-type calcium channels; it might predominantly rely on the AII receptors, IP3/ryanodine receptors, and the endoplasmic reticulum calcium store as well as calcium ATPase.