Ca2+-activated K+ channels modulate basal and E2β-induced rises in uterine blood flow in ovine pregnancy

Charles R. Rosenfeld, David N. Cornfield, Timothy Roy

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Uterine blood flow (UBF) increases >30-fold during ovine pregnancy. During the last trimester, this reflects vasodilation, which may be due to placentally derived estrogens. In nonpregnant ewes, estradiol-17β (E2β) increases UBF > 10-fold by activating nitric oxide synthase and large conductance calcium-dependent potassium channels (BKCa). To determine whether BKCa channels modulate basal and E2β-induced increases in UBF, studies were performed in near-term pregnant ewes with uterine artery flow probes and catheters for intra-arterial infusions of tetraethylammonium (TEA), a selective BKCa channel antagonist at < 1 mM, in the absence or presence of E2β (1 μg/kg iv). Uterine arteries were collected to measure BKCa channel mRNA. TEA (0.15 mM) decreased basal UBF (P < 0.0001) 40 ± 8% and 55 ± 7% (n = 11) at 60 and 90 min, respectively, and increased resistance 175 ± 48% without affecting (P > 0.1) mean arterial pressure (MAP), heart rate, or contralateral UBF. Systemic E2β increased UBF 30 ± 6% and heart rate 13 ± 1% (P ≥ 0.0001, n = 13) without altering MAP. Local TEA (0.15 mM) inhibited E2β-induced increases in UBF without affecting increases in heart rate (10 ± 4%; P = 0.006). BKCa channel mRNA was present in uterine artery myocytes from pregnant and nonpregnant ewes. Exponential increases in ovine UBF in late pregnancy may reflect BKCa channel activation, which may be mediated by placentally derived estrogens.

Original languageEnglish (US)
Pages (from-to)H422-H431
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number1 50-1
StatePublished - Oct 10 2001

Keywords

  • Estradiol-17β
  • Sheep
  • Smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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