Role of BKCa channels in regulating uterine vascular contractility: effect of high altitude hypoxia

Abstract

BKCa channels play a key role in the increased uterine artery blood flow in pregnancy. The present study tested whether chronic hypoxia attenuates pregnancy‐mediated enhanced BKCa channel activities and increases PKC‐mediated uterine vascular tone. Uterine arteries were isolated from nonpregnant (NPUA) and nearterm pregnant (PUA) sheep maintained at sea level (~300 m) or high altitude (3801 m) for 110 days. In contrast to previous studies in normoxic sheep, PKC activator PDBu‐induced contractions were increased in PUA, which was not significantly different from that of NPUA in hypoxic sheep. BKCa channel blocker TEA increased PDBu‐induced contractions in NPUA but not PUA. However, TEA increased norpinephrine (NE)‐induced contractions in both NPUA and PUA. Both BKCa channel opener, NS1619 and SKCa channel opener, NS309 caused minimal relaxations (~20%) of NPUA and PUA pre‐contracted by NE in the present or absence of endothelial cells. In addition, Western blot showed a decrease in the β1, but not α, subunit of BKCa channels in hypoxic PUA as compared with normaxic PUA. The results suggest that chronic hypoxia selectively attenuates basal uterine vascular BKCa channel activity, but not BKCa channel activation in pregnant animals, which may contribute to enhanced uterine vascular tone observed in sheep during pregnancy at high altitude hypoxia. (Supported in part by NIH grant HD31226)