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Published on: January 7, 2018
Prenatal Hypoxia Induced Dysfunction in Cerebral Arteries of Offspring Rats
Jiaqi Tang1, Na Li1, Xueyi Chen1
1Institute of Fetology, First Hospital of Soochow University, Suzhou, China.
Insights
Prenatal hypoxia impairs offspring artery function, increasing risks for adult vascular diseases. Angiotensin II (AII) constricts arteries more due to altered calcium signaling and receptors, not just L-type channels.
Area of Science:
- Cardiovascular Physiology
- Developmental Biology
- Pharmacology
Background:
- Pregnancy hypoxia can lead to abnormal fetal development.
- This can increase the risk of adult vascular diseases.
Purpose of the Study:
- To investigate angiotensin II (AII)-mediated vascular dysfunction in the middle cerebral arteries (MCA) of offspring exposed to prenatal hypoxia.
- To determine the underlying mechanisms of altered vasoconstriction and vasodilation.
Main Methods:
- Vascular tension, calcium channel activity, and endoplasmic reticulum calcium stores were measured in offspring MCA.
- Whole-cell patch clamping assessed voltage-dependent calcium channel currents.
- Quantitative real-time PCR analyzed mRNA expression of relevant receptors and channels.
Main Results:
- Prenatal hypoxia amplified AII-mediated MCA constriction in male offspring, involving AT1 and AT2 receptors.
- Increased baseline L-type calcium channel activity was observed, but AII-stimulated currents were unchanged.
- IP3/ryanodine receptor-operated channels, ER calcium stores, and SERCA activity were elevated.
- Hypoxia impaired endothelium-derived nitric oxide synthase (eNOS)-mediated vasodilation.
- mRNA levels of AT1A, AT1B, AT2R, Cav1.2α1C, Cav3.2α1H, and RyR2 were upregulated.
Conclusions:
- Pregnancy hypoxia induces both contractile and dilatory dysfunction in offspring MCA.
- AII-induced constriction is primarily mediated by AII receptors, IP3/ryanodine receptors, ER calcium stores, and calcium ATPase, rather than solely L-type and T-type calcium channels.
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.
