title: Estradiol increases urethral tone through the local inhibition of neuronal nitric oxide synthase expression.
abstract: Estrogens are known to modulate lower urinary tract (LUT) trophicity and neuronal nitric oxide synthase (nNOS) expression in several organs. The aim of this study was to explore the effects of endogenous and supraestrus levels of 17beta-estradiol (E2) on LUT and urethral nNOS expression and function. LUT function and histology and urethral nNOS expression were studied in adult female mice subjected either to sham surgery, surgical castration, or castration plus chronic E2 supplementation (80 microg.kg(-1).day(-1), i.e., pregnancy level). The micturition pattern was profoundly altered by long-term supraestrus levels of E2 with decreased frequency paralleled by increased residual volumes higher than those of ovariectomized mice. Urethral resistance was increased twofold in E2-treated mice, with no structural changes in urethra, supporting a pure tonic mechanism. Acute nNOS inhibition by 7-nitroindazole decreased frequency and increased residual volumes in ovariectomized mice but had no additive effect on the micturition pattern of long-term supraestrus mice, showing that long-term supraestrus E2 levels and acute inhibition of nNOS activity had similar functional effects. Finally, E2 decreased urethral nNOS expression in ovariectomized mice. Long-term supraestrus levels of E2 increased urethral tone through inhibition of nNOS expression, whereas physiological levels of E2 had no effect.
authors.affiliation: Service d'Urologie, Transplantation Rénale et Andrologie, Centre Hospitalier Universitaire Rangueil, TSA 50032, 31059 Toulouse, France. xaviergame@hotmail.com
authors.forename: Xavier
authors.initials: X
authors.lastname: Gamé
authors.forename: Julien
authors.initials: J
authors.lastname: Allard
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Escourrou
authors.forename: Pierre
authors.initials: P
authors.lastname: Gourdy
authors.forename: Ivan
authors.initials: I
authors.lastname: Tack
authors.forename: Pascal
authors.initials: P
authors.lastname: Rischmann
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Arnal
authors.forename: Bernard
authors.initials: B
authors.lastname: Malavaud
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D004971:Estrus / Q000502:physiology; D005260:Female; D007191:Indazoles / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009129:Muscle Tonus / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D014521:Urethra / Q000033:anatomy & histology / Q000187:drug effects* / Q000201:enzymology*; D001743:Urinary Bladder / Q000187:drug effects; D014554:Urination / Q000187:drug effects
chemical_list: D007191:Indazoles; D020030:Nitric Oxide Donors; D004958:Estradiol; D052248:Nitric Oxide Synthase Type I; C080122:7-nitroindazole