{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T03:43:39Z","timestamp":1774323819561,"version":"3.50.1"},"reference-count":59,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2005,10]]},"abstract":"<jats:p>Daily estradiol-17\u03b2 (E<jats:sub>2<\/jats:sub>\u03b2) increases basal uterine blood flow (UBF) and enhances acute E<jats:sub>2<\/jats:sub>\u03b2-mediated increases in UBF in ovariectomized nonpregnant ewes. The acute E<jats:sub>2<\/jats:sub>\u03b2-mediated rise in UBF involves vascular smooth muscle (VSM) large-conductance Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup>channels (BK<jats:sub>Ca<\/jats:sub>). BK<jats:sub>Ca<\/jats:sub>consist of pore-forming \u03b1-subunits and regulatory \u03b2<jats:sub>1<\/jats:sub>-subunits that modulate channel function and E<jats:sub>2<\/jats:sub>\u03b2 responsiveness. It is unclear whether E<jats:sub>2<\/jats:sub>\u03b2 also alters subunit expression and thus channel density and\/or function, thereby contributing to the rise in basal UBF and enhanced UBF responses that follow daily E<jats:sub>2<\/jats:sub>\u03b2. Therefore, we examined BK<jats:sub>Ca<\/jats:sub>subunit expression by using reverse transcription-PCR and immunoblot analysis of arterial VSM from reproductive and nonreproductive tissues and myometrium from ovariectomized nonpregnant ewes after daily E<jats:sub>2<\/jats:sub>\u03b2 (1 \u03bcg\/kg iv) or vehicle without or with acute E<jats:sub>2<\/jats:sub>\u03b2 (1 \u03bcg\/kg). Tissue distribution was determined by immunohistochemistry. Acute E<jats:sub>2<\/jats:sub>\u03b2 did not alter \u03b1- or \u03b2<jats:sub>1<\/jats:sub>-subunit expression in any tissue ( P &gt; 0.1). Daily E<jats:sub>2<\/jats:sub>\u03b2 also did not affect \u03b1-subunit mRNA or protein in any tissue ( P &gt; 0.1) or mesenteric arterial VSM \u03b2<jats:sub>1<\/jats:sub>-subunit. However, daily E<jats:sub>2<\/jats:sub>\u03b2 increased uterine and mammary arterial VSM \u03b2<jats:sub>1<\/jats:sub>-subunit mRNA by 32% and 83% ( P &lt; 0.05), uterine VSM protein by 30%, and myometrial \u03b2<jats:sub>1<\/jats:sub>-subunit mRNA and protein by 74% ( P \u2264 0.005). Immunostaining of uterine arteries, myometrium, and intramyometrial arteries paralleled immunoblot analyses for both subunits. Although BK<jats:sub>Ca<\/jats:sub>density is unaffected by daily and acute E<jats:sub>2<\/jats:sub>\u03b2, daily E<jats:sub>2<\/jats:sub>\u03b2 increases \u03b2<jats:sub>1<\/jats:sub>-subunit in proximal and distal uterine arterial VSM. Thus prolonged E<jats:sub>2<\/jats:sub>\u03b2 exposure may alter BK<jats:sub>Ca<\/jats:sub>function, estrogen responsiveness, and basal vascular tone and reactivity in reproductive arteries by modifying \u03b1:\u03b2<jats:sub>1<\/jats:sub>stoichiometry.<\/jats:p>","DOI":"10.1152\/ajpheart.01174.2004","type":"journal-article","created":{"date-parts":[[2005,5,28]],"date-time":"2005-05-28T02:06:43Z","timestamp":1117246003000},"page":"H1417-H1427","source":"Crossref","is-referenced-by-count":44,"title":["Estrogen regulates \u03b2<sub>1<\/sub>-subunit expression in Ca<sup>2+<\/sup>-activated K<sup>+<\/sup>channels in arteries from reproductive tissues"],"prefix":"10.1152","volume":"289","author":[{"given":"Deepa","family":"Nagar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-tie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles R.","family":"Rosenfeld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000100068.43006.36"},{"key":"R2","doi-asserted-by":"crossref","unstructured":"Benkusky NA, Fergus DJ, Zucchero TM, and England SK.Regulation of the Ca2+-sensitive domains of the maxi-K channel in the mouse myometrium during gestation.J Biol Chem275: 27712\u201327719, 2000.","DOI":"10.1074\/jbc.M000974200"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)03011-9"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1996.tb01172.x"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1038\/35038011"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(96)00230-6"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1530\/rep.0.1260043"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(65)90462-X"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000103309.55054.3E"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.116.3.411"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1080\/mic.9.4.243.257"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1997.272.6.H2765"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104689200"},{"key":"R14","doi-asserted-by":"crossref","unstructured":"Dick GM, Rossow CF, Smirnov S, Horowitz B, and Sanders KM.Tamoxifen activates smooth muscle BK channels through the regulatory \u03b21subunit.J Biol Chem26: 34594\u201334599, 2001.","DOI":"10.1074\/jbc.M104689200"},{"key":"R15","doi-asserted-by":"crossref","unstructured":"Hanner M, Vianna-Jorge R, Kamassah A, Schmalhofer WA, Knaus HG, Kaczorowski GJ, and Garcia ML.The \u03b2 subunit of the high conductance calcium-activated potassium channel. Identification of residues involved in charybdotoxin bindingJ Biol Chem26: 16289\u201316296, 1998.","DOI":"10.1074\/jbc.273.26.16289"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(02)00136-3"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1016\/S1367-5931(99)80066-0"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1007\/BF02110699"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(73)90552-8"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.38.22434"},{"key":"R21","doi-asserted-by":"crossref","unstructured":"Knaus HG, Folander K, Garcia-Calvo M, Garcia ML, Kaczorowski GJ, Smith M, and Swanson R.Primary sequence and immunological characterization of \u03b2-subunit of high conductance Ca2+-activated K+channel from smooth muscle.J Biol Chem269: 17274\u201317278, 1994.","DOI":"10.1016\/S0021-9258(17)32551-6"},{"key":"R22","doi-asserted-by":"crossref","unstructured":"Knaus HG, Garcia-Calvo M, Kaczorowski GJ, and Garcia ML.Subunit composition of the high conductance calcium-activated potassium channel from smooth muscle, a representative ofmSloandslowpokefamily of potassium channels.J Biol Chem269: 3921\u20133924, 1994.","DOI":"10.1016\/S0021-9258(17)41720-0"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-2115(97)00104-8"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1989.256.4.E536"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(86)80047-3"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1993.265.5.E690"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.275.3.H731"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.010454"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(96)00151-2"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.25.14066"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(85)90080-8"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21388"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.268.4.C799"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.115.6.719"},{"key":"R35","unstructured":"Orio P, Rojas P, Ferreira G, and Latorre R.New disguises for an old channel: MaxiK channel \u03b2-subunits.News Physiol Sci17: 156\u2013161, 2002."},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1016\/S1050-1738(01)00146-3"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000124921.81025.1F"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110057"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(84)90721-X"},{"key":"R40","unstructured":"Rosenfeld CRand Roy T.Large conductance potassium channels (BKCa) regulate basal uteroplacental blood flow during ovine pregnancy.J Soc Gynecol Investig11: 196A, 2004."},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1016\/S1071-5576(03)00049-2"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.281.1.H422"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119022"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(76)90064-8"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-3623(02)00135-0"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.1.H319"},{"key":"R47","unstructured":"Rosenfeld CR.Consideration of the uteroplacental circulation in intrauterine growth.Semin Perinatol8: 42\u201351, 1984."},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.281.4.R1025"},{"key":"R49","unstructured":"Rosenfeld CR.The Uterine Circulation.Ithaca, NY: Perinatology, 1989, p. 113\u2013134, 135\u2013156, 208\u2013238, 239\u2013271."},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.278.6.H2134"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)01394-0"},{"key":"R52","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.545bj.x"},{"key":"R53","doi-asserted-by":"crossref","unstructured":"Toro L, Wallner M, Meera P, and Tanaka Y.Maxi-KCa, a unique member of the voltage-gated K channel superfamily.News Physiol Sci13: 112\u2013117, 1998.","DOI":"10.1152\/physiologyonline.1998.13.3.112"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.275.5.H1845"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5435.1929"},{"key":"R56","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(11)91597-X"},{"key":"R57","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-05-01550.2002"},{"key":"R58","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.79.5.1024"},{"key":"R59","doi-asserted-by":"crossref","unstructured":"White RE, Darkow DJ, and Lang JL.Estrogen relaxes coronary arteries by opening BKCachannels through a cGMP-dependent mechanism.Circ Res77: 936\u2013942, 1994.","DOI":"10.1161\/01.RES.77.5.936"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.01174.2004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,11]],"date-time":"2021-07-11T07:55:07Z","timestamp":1625990107000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.01174.2004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,10]]},"references-count":59,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2005,10]]}},"alternative-id":["10.1152\/ajpheart.01174.2004"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.01174.2004","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,10]]}}}