TY - JOUR
T1 - Large conductance Ca2+-activated K+ channels contribute to vascular function in nonpregnant human uterine arteries
AU - Rosenfeld, Charles R.
AU - Word, R. Ann
AU - DeSpain, Kevin
AU - Liu, Xiao Tie
PY - 2008/9
Y1 - 2008/9
N2 - Large conductance K+ channels (BKCa) are expressed in uterine artery (UA) smooth muscle from nonpregnant and pregnant sheep and contribute to the regulation of basal vascular tone and responses to estrogen and vasoconstrictors. To determine if BKCa are expressed in women and contribute to UA function, we collected UA from nonpregnant women (n = 31) at elective hysterectomy and analyzed for subunit protein, localization with immunohistochemistry, and function using endothelium-denuded rings. UA expresses BKCa α -, β1- and β2-subunit protein. KCl and phenylephrine (PE, an α1-agonist) caused dose-dependent vasoconstriction (P <.001), and UA precontracted with PE dose-dependently relaxed with sodium nitroprusside (SNP; P <.001).Tetraethylammonium chloride (TEA, 0.2-1.0 mM), a BKCa inhibitor, dose-dependently increased resting tone (P =.004; 28% ± 5.3% with 1.0 mM), enhanced PE-induced (10-6 M) vasoconstriction (P < .04), and attenuated SNP-induced relaxation at 1.0 mM (P =.02). BKCa are expressed in human UA and modulate vascular function by attenuating vasoconstrictor responses and contributing to nitric oxide-induced vasorelaxation.
AB - Large conductance K+ channels (BKCa) are expressed in uterine artery (UA) smooth muscle from nonpregnant and pregnant sheep and contribute to the regulation of basal vascular tone and responses to estrogen and vasoconstrictors. To determine if BKCa are expressed in women and contribute to UA function, we collected UA from nonpregnant women (n = 31) at elective hysterectomy and analyzed for subunit protein, localization with immunohistochemistry, and function using endothelium-denuded rings. UA expresses BKCa α -, β1- and β2-subunit protein. KCl and phenylephrine (PE, an α1-agonist) caused dose-dependent vasoconstriction (P <.001), and UA precontracted with PE dose-dependently relaxed with sodium nitroprusside (SNP; P <.001).Tetraethylammonium chloride (TEA, 0.2-1.0 mM), a BKCa inhibitor, dose-dependently increased resting tone (P =.004; 28% ± 5.3% with 1.0 mM), enhanced PE-induced (10-6 M) vasoconstriction (P < .04), and attenuated SNP-induced relaxation at 1.0 mM (P =.02). BKCa are expressed in human UA and modulate vascular function by attenuating vasoconstrictor responses and contributing to nitric oxide-induced vasorelaxation.
KW - Basal tone
KW - Myometrium
KW - Nitric oxide
KW - α-agonists
KW - β1/β2- regulatory subunits
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U2 - 10.1177/1933719108319160
DO - 10.1177/1933719108319160
M3 - Article
C2 - 18836130
AN - SCOPUS:52449128966
SN - 1933-7191
VL - 15
SP - 651
EP - 660
JO - Reproductive Sciences
JF - Reproductive Sciences
IS - 7
ER -