Title

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

Document Type

Article

Publication Date

2000

Abstract

Nitric oxide synthase (NOS) contributes to estradiol-17ß (E2ß)-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) E2ß activates these channels, and 3) channel blockade plus NOS inhibition alters E2ß-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 E2ß 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 E2ß-induced uterine vasodilation (n = 37, R = 0.77, P < 0.0001), with maximum inhibition averaging 67 ± 11%. Mean arterial pressure (MAP) and E2ß-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 E2ß-induced uterine vasodilation without affecting MAP and E2ß-induced increases in contralateral UBF and heart rate. Acute E2ß-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.

Publication Title

American Journal of Physiology - Heart and Circulatory Physiology

Volume

279

Issue

1 48-1

First Page

H319

Last Page

H328

Comments

This article was published in American Journal of Physiology - Heart and Circulatory Physiology, Volume 279, Issue 1 48-1, Pages H319-H328.

The published version is available at http://ajpheart.physiology.org/content/279/1/H319.

Copyright © 2000 APS.

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