Regulation of the cGMP-cPKG pathway and large-conductance Ca 3+-activated K+ channels in uterine arteries during the ovine ovarian cycle

Liaqat H. Khan, Charles R. Rosenfeld, Xiao Tie Liu, Ronald R. Magness

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The follicular phase of the ovine ovarian cycle demonstrates parallel increases in ovarian estrogens and uterine blood flow (UBF). Although estrogen and nitric oxide contribute to the rise in UBF, the signaling pathway remains unclear. We examined the relationship between the rise in UBF during the ovarian cycle of nonpregnant sheep and changes in the uterine vascular cGMP-dependent pathway and large-conductance Ca2+-activated K+ channels (BKCa). Nonpregnant ewes (n = 19) were synchronized to either follicular or luteal phase using a vaginal progesterone-releasing device (CIDR), followed by intramuscular PGF, CIDR removal, and treatment with pregnant mare serum gonadotropin. UBF was measured with flow probes before tissue collection, and second-generation uterine artery segments were collected from nine follicular and seven luteal phase ewes. The poreforming α- and regulatory β-subunits that constitute the BK, soluble guanylyl cyclase (sGC), and cGMP-dependent protein kinase G (cPKG) isoforms (cPKG and cPKG) were measured by Western analysis and cGMP levels by RIA. BKCa subunits were localized by immunohistochemistry. UBF rose >3-fold (P - < 0.04) in follicular phase ewes, paralleling a 2.3-fold rise in smooth muscle cGMP and 32% increase in cPKG (P < 0.05). sGC, cPKG, and the BKCa α-subunit were unchanged. Notably, expression of β1- and β2-regulatory subunits rose 51 and 79% (P ≤ 0.05), respectively. Increases in endogenous ovarian estrogens in follicular-phase ewes result in increases in UBF associated with upregulation of the cGMP- and cPKG-dependent pathway and increased vascular BKCa β/α-subunit stoichiometry, suggesting enhanced BKCa activation contributes to the follicular phase rise in UBF.

Original languageEnglish (US)
Pages (from-to)E222-E228
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume298
Issue number2
DOIs
StatePublished - Feb 1 2010

Keywords

  • Estrogen
  • Guanylyl cyclase
  • Protein kinase G
  • Uterine blood flow

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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