Gestational hypoxia up-regulates protein kinase C and inhibits calcium-activated potassium channels in ovine uterine arteries.

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.

• Authors: Daliao Xiao, Ronghui Zhu, Lubo Zhang
• Journal: International journal of medical sciences (Int J Med Sci) Vol. 11 Issue 9 Pg. 886-92 ( 2014) ISSN: 1449-1907 [Electronic] Australia
• PMID: 25013368 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Potassium Channels, Calcium-Activated
• Phorbol 12,13-Dibutyrate
• Protein Kinase C

Topics

• Animals
• Female
• Humans
• Hypoxia (physiopathology)
• Organ Culture Techniques
• Phorbol 12,13-Dibutyrate (administration & dosage)
• Potassium Channels, Calcium-Activated (antagonists & inhibitors, metabolism)
• Pregnancy
• Protein Kinase C (biosynthesis)
• Sheep
• Uterine Artery (physiopathology)
• Vasodilation (drug effects)