Gestational Hypoxia Up-regulates Protein Kinase C and Inhibits Calcium-Activated Potassium Channels in Ovine Uterine Arteries
Year: 2014
Type: article
Abstract: OBJECTIVE: The present study tested the hypothesis that gestational hypoxia up-regulates protein kinase C (PKC) and inhibits calcium-activated potassium channels (KCa)-mediated relaxations of uterine arteries in pregnancy. STUDY DESIGN: Uterine arteries were isolated from nonpregnant (NPUA) and pregnant (PUA) (~140 day gestation) sheep maintained at either sea level or high altitude (3,820 m for 110 days, PaO2: 60 mmHg). Contractions of uterine arteries were determined. KEY FINDINGS: In normoxic PUA, selective inhibition of large-conductance KCa (BK) channels significantly enhanced PKC activator phorbol 12, 13-dibutyrate (PDBu)-induced contractions. This effect was abrogated by chronic hypoxia in gestation. Unlike BK channels, inhibition of small-conductance KCa (SK) channels had no significant effect on PDBu-mediated contractions. In normoxic PUA, activation of both BK with NS1619 or SK with NS309 produced concentration-dependent relaxations, which were not altered by the addition of PDBu. However, in uterine arteries treated with chronic hypoxia (10.5% O2 for 48 h), both NS1619- and NS309-induced relaxations were significantly attenuated by PDBu. In NPUAs, inhibition of BK channels significantly enhanced PDBu-induced contractions in both normoxic and hypoxic animals. CONCLUSION: The results suggest that in the normoxic condition BK inhibits PKC activity and uterine vascular contractility, which is selectively attenuated by chronic hypoxia during gestation. In addition, hypoxia induces PKC-mediated inhibition of BK and SK activities and relaxations of uterine arteries in pregnancy.
DOI: 10.7150/ijms.9338
Authors: Daliao Xiao, Ronghui Zhu, Lubo Zhang
Institutions: Loma Linda University Medical Center, Loma Linda University
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,337
Awards: G1366320854, Fetal Programming of Vascular Dysfunction by Nicotine Exposure, G4336344864, G5156455020, Steroid Hormones and Uterine Vascular Adaptation to Pregnancy, (INTRODUCTION) MECHANISMS OF ACCLIMATIZATION: FETUS AND ADULT, G7350082112, Hypoxia and Aberrant Uterine Vascular Adaptation in Pregnancy, G9000097658, G9000166619, G9000232694
OpenAlex ID: W2097249865