title: Neurotransmission and viscoelasticity in the ovine fetal bladder after in utero bladder outflow obstruction.
abstract: Fetal bladder outflow obstruction, predominantly caused by posterior urethral valves, results in significant urinary tract pathology; these lesions are the commonest cause of end-stage renal failure in children, and up to 50% continue to suffer from persistent postnatal bladder dysfunction. To investigate the physiological development of the fetal bladder and the response to urinary flow impairment, we performed partial urethral obstruction and complete urachal ligation in the midgestation fetal sheep for 30 days. By electrical and pharmacological stimulation of bladder strips, we found that muscarinic, purinergic, and nitrergic mechanisms exist in the developing fetal bladder at this gestation. After bladder outflow obstruction, the fetal bladder became hypocontractile, producing less force after nerve-mediated and muscarinic stimulation with suggested denervation, and also exhibited greater atropine resistance. Furthermore, fetal bladder urothelium exerted a negative inotropic effect, partly nitric oxide mediated, that was not present after obstruction. Increased compliance, reduced elasticity, and viscoelasticity were observed in the obstructed fetal bladder, but the proportion of work performed by the elastic component (a physical parameter of extracellular matrix) remained the same. In addition to denervation, hypocontractility may result from a reduction in the elastic modulus that may prevent any extramuscular components from sustaining force produced by detrusor smooth muscle.
authors.affiliation: Nephro-Urology Unit, Institute of Child Health, London WC1N 1EH, United Kingdom. n.thiruchelvam@ich.ucl.ac.uk
authors.forename: N
authors.initials: N
authors.lastname: Thiruchelvam
authors.forename: C
authors.initials: C
authors.lastname: Wu
authors.forename: A
authors.initials: A
authors.lastname: David
authors.forename: A S
authors.initials: AS
authors.lastname: Woolf
authors.forename: P M
authors.initials: PM
authors.lastname: Cuckow
authors.forename: C H
authors.initials: CH
authors.lastname: Fry
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004548:Elasticity; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D034561:Sheep, Domestic; D001743:Urinary Bladder / Q000196:embryology* / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology; D001748:Urinary Bladder Neck Obstruction / Q000196:embryology* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D001285:Atropine; D000241:Adenosine