title: Effect of cortisol on norepinephrine-mediated contractions in ovine uterine arteries.
abstract: Cortisol potentiated norepinephrine (NE)-mediated contractions in ovine uterine arteries (UA). We tested the hypothesis that cortisol regulated alpha(1)-adrenoceptor-mediated pharmacomechanical coupling differentially in nonpregnant UA (NUA) and pregnant UA (PUA). Cortisol (10 ng/ml for 24 h) significantly increased contractile coupling efficiency of alpha(1)-adrenoceptors in NUA, but increased alpha(1)-adrenoceptor density in PUA. Cortisol potentiated NE-induced inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] synthesis in both NUA and PUA, but increased coupling efficiency of alpha(1)-adrenoceptors to Ins(1,4,5)P(3) synthesis only in NUA. Carbenoxolone alone did not affect NE-mediated Ins(1,4,5)P(3) production, but significantly enhanced cortisol-mediated potentiation of NE-stimulated Ins(1,4,5)P(3) synthesis in PUA. In addition, cortisol potentiated the NE-induced increase in Ca(2+) concentration in PUA, but increased NE-mediated contraction for a given amount of Ca(2+) concentration in NUA. Collectively, the results indicate that cortisol potentiates NE-mediated contractions differentially in NUA and PUA, i.e., by upregulating alpha(1)-adrenoceptor density leading to increased Ca(2+) mobilization in PUA while increasing alpha(1)-adrenoceptor coupling efficiency and myofilament Ca(2+) sensitivity in NUA. In addition, the results suggest that pregnancy increases type 2 11 beta-hydroxysteroid dehydrogenase activity in the UA.
authors.affiliation: Center for Perinatal Biology, Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, California 92350, USA.
authors.forename: Daliao
authors.initials: D
authors.lastname: Xiao
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Huang
authors.forename: William J
authors.initials: WJ
authors.lastname: Pearce
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Longo
authors.forename: Lubo
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001158:Arteries / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000032:analysis / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism; D011247:Pregnancy; D018340:Receptors, Adrenergic, alpha-1 / Q000032:analysis / Q000187:drug effects / Q000502:physiology; D012756:Sheep; D014316:Tritium; D014599:Uterus / Q000098:blood supply*
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D014316:Tritium; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D006854:Hydrocortisone; D009638:Norepinephrine; D011224:Prazosin