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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/R851    most recent 00467.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Gamé, X. Articles by Malavaud, B. PubMed PubMed Citation Articles by Gamé, X. Articles by Malavaud, B.

RENAL HEMODYNAMICS AND CARDIORENAL INTEGRATION

Estradiol increases urethral tone through the local inhibition of neuronal nitric oxide synthase expression

¹Service d'Urologie, Transplantation Rénale et Andrologie, ²Institut National de la Santé et de la Recherche Médicale U858 et Laboratoire de Physiologie, and ³Laboratoire D'Anatomie Pathologique, Centre Hospitalier Universitaire Rangueil, Toulouse, France

Submitted 29 June 2007 ; accepted in final form 2 January 2008

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 17β-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 µg·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.

estrogen; neurourology; urethra