Large conductance Ca2+-activated and voltage-activated K + channels contribute to the rise and maintenance of estrogen-induced uterine vasodilation and maintenance of blood pressure

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Uterine blood flow (UBF) increases greater than 4-fold 90 min after systemic estradiol-17β (E2β) in nonpregnant sheep and remains elevated longer than 6-8 h; mean arterial pressure (MAP) is unchanged. Large-conductance Ca+2-activated (BKCa) and voltage-activated (K V) K+ channels contribute to the acute rise in UBF; their role in maintaining UBF and MAP longer than 90 min is unknown. We examined this in five nonpregnant, ovariectomized ewes with uterine artery (UA) flow probes and catheters in a UA for infusion of K+ channel inhibitors and uterine vein to sample venous effluent. Animals received systemic E2β (1.0 μg/kg; control), E2β+UA tetraethylammonium (TEA; 0.4-0.8 mM, n = 4), and E2β+UA 4-aminopyridine (4-AP; 0.01-0.08 mM, n = 4) to block BK Caand KV, respectively, while monitoring MAP, heart rate, and UBF. Uterine cGMP synthesis was measured. Ninety minutes after E2β,UBFrose 4.5-fold, uterine vascular resistance (UVR) fell greater than 5-fold and MAP was unchanged [78 ± 0.8 (SEM) vs. 77 ± 1.5 mm Hg] in control studies and before UA inhibition with TEA and 4-AP. Between 90 and 120min, UBF, UVR, and MAP were unchanged after E2β alone. E2β+TEA dose dependently decreased ipsilateral UBF and increased UVR (24 ± 8.9 and 38 ± 16%, respectively, at 0.8 mM; P < 0.03); MAP was unchanged. Contralateral UBF/UVR were unaffected. E2β+4-AP also dose dependently decreased ipsilateral UBF and increased UVR (27 ± 5.3 and 76 ± 18%, respectively, at 0.08 mM; P < 0.001); however, MAP rose 27 ±6.9% (P ≤ 0.006). E2β increased uterine cGMP synthesis greater than 3.5-fold and was unaffected by local K+ channel inhibition. BKCa and KV contribute to the rise and maintenance of E2β-induced uterine vasodilation, which is partially cGMP dependent. Systemic vascular KV also contributes to maintaining MAP after systemic E2β.

Original languageEnglish (US)
Pages (from-to)6012-6020
Number of pages9
JournalEndocrinology
Volume153
Issue number12
DOIs
StatePublished - Dec 1 2012

ASJC Scopus subject areas

  • Endocrinology

Fingerprint Dive into the research topics of 'Large conductance Ca<sup>2+</sup>-activated and voltage-activated K <sup>+</sup> channels contribute to the rise and maintenance of estrogen-induced uterine vasodilation and maintenance of blood pressure'. Together they form a unique fingerprint.

  • Cite this