NDLI: Chronic hypoxia increases pressure-dependent myogenic tone of the uterine artery in pregnant sheep: role of ERK/PKC pathway

Content Provider	PubMed Central
Author	Chang, Katherine Xiao, Daliao Huang, Xiaohui Longo, Lawrence D. Zhang, Lubo
Copyright Year	2009
Abstract	Chronic hypoxia during pregnancy has profound effects on uterine artery (UA) contractility and attenuates uterine blood flow. The present study tested the hypothesis that chronic hypoxia inhibits the pregnancy-induced reduction in pressure-dependent myogenic tone of resistance-sized UAs. UAs were isolated from nonpregnant ewes (NPUAs) and near-term pregnant ewes (PUAs) that had been maintained at sea level (∼300 m) or at high altitude (3,801 m) for 110 days. In normoxic animals, the pressure-dependent myogenic response was significantly attenuated in PUAs compared with NPUAs. Hypoxia significantly increased myogenic tone in PUAs and abolished its difference between PUAs and NPUAs. Consistently, there was a significant increase in PKC-mediated baseline Ca2+ sensitivity of PUAs in hypoxic animals. Hypoxia significantly increased phorbol 12,13-dibutyrate (PDBu)-induced contractions in PUAs but not in NPUAs. Whereas the inhibition of ERK1/2 by PD-98059 potentiated PDBu-mediated contractions of PUAs in normoxic animals, it failed to do so in hypoxic animals. Hypoxia decreased ERK1/2 expression in PUAs. PDBu induced membrane translocation of PKC-α and PKC-ɛ. Whereas there were no significant differences in PKC-α translocation among all groups, the translocation of PKC-ɛ was significantly enhanced in NPUAs compared with PUAs in normoxic animals, and hypoxia significantly increased PKC-ɛ translocation in PUAs. In the presence of PD-98059, there were no significant differences in PDBu-induced PKC-ɛ translocation among all groups. Treatment of PUAs isolated from normoxic animals with 10.5% O2 for 48 h ex vivo significantly increased PDBu-induced contractions and eliminated its difference between PUAs and NPUAs. The results suggest that hypoxia upregulates pressure-dependent myogenic tone through its direct effect in suppressing ERK1/2 activity and increasing the PKC signal pathway, leading to an increase in the Ca2+ sensitivity of the myogenic mechanism in the UA during pregnancy.
Related Links	http://dx.doi.org/10.1152/ajpheart.00090.2009
Starting Page	1840
File Format	PDF
ISSN	03636135
e-ISSN	15221539
Journal	American Journal of Physiology - Heart and Circulatory Physiology
Issue Number	6
Volume Number	296
Language	English
Publisher	American Physiological Society
Publisher Date	2009-06-01
Access Restriction	Open
Rights Holder	American Physiological Society
Subject Keyword	Physiology (medical) Physiology Cardiology and Cardiovascular Medicine Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical) Cardiology and Cardiovascular Medicine

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