Prenatal Hypoxia Induced Dysfunction In Cerebral Artery Of Adult Offspring-via Ang?/Calcium Channels

Background Hypoxia during pregnancy could cause abnormal development and lead to increased risks of vascular diseases in adults.This study determined angiotensin ??Ang??-mediated vascular dysfunction in adult offspring middle cerebral arteries?MCA?.Methods Pregnant rats were exposed to hypoxia.Vascular tension in offspring MCA was tested by Ang?with or without inhibitors.Calcium channel activities and endoplasmic reticulum calcium stores were tested.Whole-cell patch clamp was used to investigate voltage-dependent calcium channel currents.The mRNA expression was tested using quantitative real-time polymerase chain reaction.Results Ang?-mediated MCA constriction was greater in male adult offspring exposed to prenatal hypoxia.AT1 and AT2 receptors were involved in the altered Ang?-mediated vasoconstriction.Prenatal hypoxia increased baseline activities of L-type calcium channel currents in MCA smooth muscle cells.However,calcium currents stimulated by Ang?were not significantly changed,nifedipine inhibited Ang?-mediated vasoconstrictions in the MCA.Activities of IP₃/ryanodine receptor–operated calcium channels,endoplasmic reticulum calcium stores,and sarco-endoplasmic reticulum membrane Ca²⁺-ATPase were increased.Prenatal hypoxia also caused dysfunction of vasodilatation via the endothelial NO synthase.The mRNAexpressions of AT1 A,AT1B,AT2 R,Cav1.2?1C,Cav3.2?1H,and Ryr2 were increased in the prenatal hypoxia group.Conclusions Hypoxia in pregnancy could induce dysfunction in both contraction and dilation in the offspring MCA.Ang?-increased constriction in the prenatal hypoxia group was not mainly dependent on the L-type or T-type calcium channels,it might predominantly rely on the Ang?receptors,IP₃/ryanodine receptors,and the endoplasmic reticulum calcium store as well as Ca²⁺-ATPase.