title: Ca(2+)-activated K(+) channels modulate basal and E(2)beta-induced rises in uterine blood flow in ovine pregnancy.
abstract: Uterine blood flow (UBF) increases >30-fold during ovine pregnancy. During the last trimester, this reflects vasodilation, which may be due to placentally derived estrogens. In nonpregnant ewes, estradiol-17 beta (E(2)beta) increases UBF >10-fold by activating nitric oxide synthase and large conductance calcium-dependent potassium channels (BK(Ca)). To determine whether BK(Ca) channels modulate basal and E(2)beta-induced increases in UBF, studies were performed in near-term pregnant ewes with uterine artery flow probes and catheters for intra-arterial infusions of tetraethylammonium (TEA), a selective BK(Ca) channel antagonist at <1 mM, in the absence or presence of E(2)beta (1 microg/kg iv). Uterine arteries were collected to measure BK(Ca) channel mRNA. TEA (0.15 mM) decreased basal UBF (P < 0.0001) 40 +/- 8% and 55 +/- 7% (n = 11) at 60 and 90 min, respectively, and increased resistance 175 +/- 48% without affecting (P > 0.1) mean arterial pressure (MAP), heart rate, or contralateral UBF. Systemic E(2)beta increased UBF 30 +/- 6% and heart rate 13 +/- 1% (P < or = 0.0001, n = 13) without altering MAP. Local TEA (0.15 mM) inhibited E(2)beta-induced increases in UBF without affecting increases in heart rate (10 +/- 4%; P = 0.006). BK(Ca) channel mRNA was present in uterine artery myocytes from pregnant and nonpregnant ewes. Exponential increases in ovine UBF in late pregnancy may reflect BK(Ca) channel activation, which may be mediated by placentally derived estrogens.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9063, USA. crosen@mednet.swmed.edu
authors.forename: C R
authors.initials: CR
authors.lastname: Rosenfeld
authors.forename: D N
authors.initials: DN
authors.lastname: Cornfield
authors.forename: T
authors.initials: T
authors.lastname: Roy
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012756:Sheep; D019789:Tetraethylammonium / Q000494:pharmacology; D014599:Uterus / Q000098:blood supply*; D014664:Vasodilation
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D004958:Estradiol; D019789:Tetraethylammonium