title: Estrogen induces angiogenesis of the female rabbit bladder.
abstract: Postmenopausal bladder dysfunction has been speculated to involve decreased circulating estrogen levels. It is our hypothesis that estrogen induces bladder dysfunctions by modulating blood flow to the bladder, i.e. low estrogen reduces blood flow to the bladder, whereas high estrogen increases blood flow. Our previous studies have demonstrated that estrogen administration in female rabbits induces a 'functional hypertrophy' of the urinary bladder smooth muscle represented by increased smooth muscle mass, which corresponds to increased contractile responses to all forms of stimulation. The present study investigates the effect of estrogen on vasculature density and distribution. Twenty-four female New Zealand white rabbits were separated into six groups of four rabbits each. Group 1 served as controls. Groups 2-6 were ovariectomized. Two weeks after ovariectomy (Ovx), groups 3-6 were given 17-beta estradiol (1 mg/kg per day) by s.c. implant for 1, 3, 7, and 14 days respectively. Blood vessel density and distribution were evaluated by immunohistochemistry and quantitative image analyses. Ovx resulted in significant vascular degeneration and decreased density, whereas estradiol administration mediated a significant angiogenic effect characterized by increased vascular density, and distribution of new vasculature within the smooth muscle bundles of the detrusor. Estradiol-induced vasculogenesis corresponds with our previously demonstrated increase in blood flow to the bladder and increased contractility. The most interesting aspect of these studies is the increased vascularization localized within the muscle bundles rather than between the muscle bundles, which may be important in the link between estrogen and increased incidence of cancers.
authors.affiliation: Albany College of Pharmacy, Albany, New York 12208, USA.
authors.forename: Alpha Dian-Yu
authors.initials: AD
authors.lastname: Lin
authors.forename: Anita
authors.initials: A
authors.lastname: Mannikarottu
authors.forename: Barry A
authors.initials: BA
authors.lastname: Kogan
authors.forename: Catherine
authors.initials: C
authors.lastname: Whitbeck
authors.forename: Paul
authors.initials: P
authors.lastname: Chichester
authors.forename: Robert E
authors.initials: RE
authors.lastname: Leggett
authors.forename: Robert M
authors.initials: RM
authors.lastname: Levin
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western / Q000379:methods; D004343:Drug Implants; D004730:Endothelium, Vascular / Q000737:chemistry / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D007150:Immunohistochemistry / Q000379:methods; D009389:Neovascularization, Pathologic; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011817:Rabbits; D001743:Urinary Bladder / Q000033:anatomy & histology / Q000098:blood supply* / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D015415:Biomarkers; D004343:Drug Implants; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D004958:Estradiol