Large-conductance Ca2+-dependent K+ channels regulate basal uteroplacental blood flow in ovine pregnancy

Charles R. Rosenfeld, Tim Roy, Kevin DeSpain, Blair E. Cox

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

OBJECTIVES: The mechanisms regulating basal uteroplacental blood flow (UBF) and the greater than 30-fold increase observed in normal pregnancy remain unclear. Although vascular growth contributes in early gestation, vasodilation accounts for the exponential rise seen in the last third of pregnancy. Large conductance potassium channels (BKCa) are expressed in uterine vascular smooth muscle (VSM), but the extent of their role in regulating UBF in pregnancy is unclear. Therefore, we determined if BKCa regulate basal UBF during ovine pregnancy. METHODS: Studies were performed at 113 to 127 days and 135 to 150 days of gestation in eight pregnant ewes instrumented with uterine artery flow probes and uterine arterial and venous catheters. Tetraethylammonium chloride (TEA), a BKCa-specific inhibitor at less than 1.0 mM, was infused intra-arterially into the pregnant uterine horn over 60 minutes to achieve levels of 0.001-0.35 mM while continuously monitoring UBF, arterial pressure (MAP), and heart rate (HR). Uterine arterial and venous blood was collected simultaneously to measure uterine cyclic guanosine monophosphate (cGMP) synthesis. RESULTS: Intra-arterial TEA dose-dependently decreased basal UBF in the early (R = 0.81, n = 36, P <.001) and late (R = 0.72, n = 31, P <.001) study periods without altering contralateral UBF, MAP, and HR. The IC50 was 0.2 mM and basal UBF decreased <80% at 0.35 mM in both periods. Although UBF fell greater than 40% at estimated plasma TEA levels of 0.3 mM, uterine arterial cGMP was unchanged, uterine venous cGMP rose, and uterine cGMP synthesis was unchanged; therefore, upstream events associated with BKCa activation were unaffected by blockade. CONCLUSIONS: These are the first data demonstrating that BKCa are essential in the maintenance of basal UBF in the last third of ovine pregnancy.

Original languageEnglish (US)
Pages (from-to)402-408
Number of pages7
JournalJournal of the Society for Gynecologic Investigation
Volume12
Issue number6
DOIs
StatePublished - Sep 1 2005

Keywords

  • Potassium channels
  • Sheep
  • Uterine cGMP
  • Uterine vasodilation

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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