Large conductance Ca2+-activated K+ channels contribute to vascular function in nonpregnant human uterine arteries.
Large conductance K( +) channels (BK(Ca)) 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 BK(Ca) 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 BK(Ca) alpha -, beta1- and beta2-subunit protein. KCl and phenylephrine (PE, an alpha(1)-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 BK(Ca) 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). BK( Ca) are expressed in human UA and modulate vascular function by attenuating vasoconstrictor responses and contributing to nitric oxide-induced vasorelaxation.
Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, TX 75390, USA. charles.rosenfeld@utsouthwestern.edu
Charles R
CR
Rosenfeld
R Ann
RA
Word
Kevin
K
DeSpain
Xiao-tie
XT
Liu
D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D014599:Uterus / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D051036:Large-Conductance Calcium-Activated Potassium Channels; D010656:Phenylephrine