Mechanisms modulating estrogen-induced uterine vasodilation

Charles R. Rosenfeld, Timothy Roy, Blair E. Cox

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Estrogen, a potent vasodilator, has its greatest effects in reproductive tissues, e.g., increasing uterine blood flow (UBF) 5- to 10-fold within 90 min after a bolus dose. High-conductance potassium channels and nitric oxide (NO) contribute to the uterine responses, but other factors may be involved. We examined the role of ATP-dependent (ATP-sensitive) and voltage-gated (Kv) potassium channels and new protein synthesis in ovariectomized ewes with uterine artery flow probes, infusing intraarterial inhibitors glibenclamide (GLB; KATP), 4-aminopyridine (4-AP; Kv) or cycloheximide, respectively, into one uterine horn before and/or after systemic estradiol-17β (E2β, 1 μg/kg iv). E2β alone increased UBF >5-fold and heart rate by 10-25% (P<.01) within 90 min; mean arterial pressure (MAP) was unaffected. GLB did not alter basal hemodynamic parameters or responses to E2β. Basal UBF and heart rate were unaffected by 4-AP, but MAP increased by 10% and 25% at 30 and 120 min of infusion (P<.01), respectively. Although E2β-induced rises in UBF were unaffected in the control uterine horn, 4-AP dose-dependently inhibited UBF responses in the infused horn (R=.83, P=.003, n=10). Cycloheximide not only dose-dependently inhibited UBF responses (R=.57, P=.01, n=18) and increases in uterine cGMP secretion, 23.4±10.7 versus 340±60 pmol/min (P<.001), but also decreased UBF by 50% and cGMP by ∼90% at the time of maximum UBF. Mechanisms modulating estrogen-induced uterine vasodilation involve signaling pathways that include NO, smooth muscle cGMP, smooth muscle potassium channels and new protein synthesis.

Original languageEnglish (US)
Pages (from-to)115-125
Number of pages11
JournalVascular Pharmacology
Volume38
Issue number2
DOIs
StatePublished - Feb 1 2002

Keywords

  • Nitric oxide
  • Potassium channels
  • Sheep
  • Uterine blood flow

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

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