Calcium-activated potassium channels and nitric oxide coregulate estrogen-induced vasodilation

Charles R. Rosenfeld, Richard E. White, Tim Roy, Blair E. Cox

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Nitric oxide synthase (NOS) contributes to estradiol-17β (E2β)-induced uterine vasodilation, but additional mechanisms are involved, and the cellular pathways remain unclear. We determined if 1) uterine artery myocytes express potassium channels, 2) E2β activates these channels, and 3) channel blockade plus NOS inhibition alters E2β-induced uterine vasodilation. Studies of cell-attached patches identified a 107 ± 7 pS calcium-dependent potassium channel (BK(Ca)) in uterine artery myocytes that rapidly increased single-channel open probability 70-fold (P < 0.05) after exposure to 100 nM E2β through an apparent cGMP-dependent mechanism. In ovari-ectomized nonpregnant ewes (n = 11) with uterine artery flow probes and catheters, local BK(Ca) blockade with tetraethylammonium (TEA; 0.05-0.6 mM) dose dependently inhibited E2β-induced uterine vasodilation (n = 37, R = 0.77, P < 0.0001), with maximum inhibition averaging 67 ± 11%. Mean arterial pressure (MAP) and E2β-induced increases (P ≤ 0.001) in heart rate (13%) and contralateral uterine blood flow (UBF, ~5-fold) were unaffected. Local NOS inhibition plus BK(Ca) blockade, using submaximal doses of nitro-L-arginine methyl ester (5 mg/ml) and TEA (0.3 mM), did not alter basal UBF but completely inhibited ipsilateral E2β-induced uterine vasodilation without affecting MAP and E2β-induced increases in contralateral UBF and heart rate. Acute E2β-mediated uterine vasodilation involves rapid activation of uterine artery BK(Ca) and NOS, and the pathway for their interaction appears to include activation of guanylyl cyclase.

Original languageEnglish (US)
Pages (from-to)H319-H328
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number1 48-1
DOIs
StatePublished - 2000

Keywords

  • Estradiol-17β
  • Nonpregnant sheep
  • Uterine blood flow

ASJC Scopus subject areas

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

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