Physiologic sequelae of partial infravesical obstruction in the mouse: Role of inducible nitric oxide synthase

Gary E. Lemack, Fiona Burkhard, Philippe E. Zimmern, John D. Mcconnell, Victor K. Lin

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Purpose: To develop a mouse model for partial infravesical obstruction, and determine the resultant changes in bladder function, with particular emphasis on the role of inducible nitric oxide synthase (iNOS) in the bladder response. Materials and Methods: Wild type mice were subjected to no intervention, sham operation, and varying durations of partial outlet obstruction (1, 3, and 5 weeks). They then underwent cystometric evaluation, bladder strip stimulation studies using carbachol, and relaxation studies using l-arginine, sodium nitroprusside, and 8-bromoguanosine 3'-5' cyclic guanosine monophosphate. Bladder tissue was subjected to RT-PCR and Western analysis for iNOS. Bladders were also studied histologically using morphometric analysis. Results: Bladders from mice obstructed for 5 weeks were heavier (weight increased by 110%), larger (capacity increased by 73%), and had a higher frequency of abnormal appearing cystometric curves than normal bladders. Tissue bath studies demonstrated decreased contractility in response to cholinergic stimulation at 5 weeks of obstruction (decreased by 55% at maximal stimulation). RT-PCR demonstrated iNOS in approximately 70% of bladders obstructed for 1 and 3 weeks, while the iNOS protein was apparent in 50% of the bladders from the same groups. Conclusions: This new animal model of infravesical obstruction is reliable and reproducible. Moreover, the physiologic changes noted are comparable to other models, but an added advantage is the relevance of this model with regard to studying new transgenic or knockout mice. Enhanced expression of iNOS seen early after obstruction may serve to improve oxygenation during obstruction-induced ischemia.

Original languageEnglish (US)
Pages (from-to)1015-1022
Number of pages8
JournalJournal of Urology
Volume161
Issue number3
DOIs
StatePublished - Mar 1999

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Nitric Oxide Synthase Type II
Urinary Bladder
Guanosine Monophosphate
Polymerase Chain Reaction
Cyclic GMP
Carbachol
Nitroprusside
Baths
Knockout Mice
Cholinergic Agents
Transgenic Mice
Arginine
Ischemia
Animal Models
Weights and Measures

Keywords

  • Bladder outlet obstruction
  • Mouse
  • Nitric oxide

ASJC Scopus subject areas

  • Urology

Cite this

Physiologic sequelae of partial infravesical obstruction in the mouse : Role of inducible nitric oxide synthase. / Lemack, Gary E.; Burkhard, Fiona; Zimmern, Philippe E.; Mcconnell, John D.; Lin, Victor K.

In: Journal of Urology, Vol. 161, No. 3, 03.1999, p. 1015-1022.

Research output: Contribution to journalArticle

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abstract = "Purpose: To develop a mouse model for partial infravesical obstruction, and determine the resultant changes in bladder function, with particular emphasis on the role of inducible nitric oxide synthase (iNOS) in the bladder response. Materials and Methods: Wild type mice were subjected to no intervention, sham operation, and varying durations of partial outlet obstruction (1, 3, and 5 weeks). They then underwent cystometric evaluation, bladder strip stimulation studies using carbachol, and relaxation studies using l-arginine, sodium nitroprusside, and 8-bromoguanosine 3'-5' cyclic guanosine monophosphate. Bladder tissue was subjected to RT-PCR and Western analysis for iNOS. Bladders were also studied histologically using morphometric analysis. Results: Bladders from mice obstructed for 5 weeks were heavier (weight increased by 110{\%}), larger (capacity increased by 73{\%}), and had a higher frequency of abnormal appearing cystometric curves than normal bladders. Tissue bath studies demonstrated decreased contractility in response to cholinergic stimulation at 5 weeks of obstruction (decreased by 55{\%} at maximal stimulation). RT-PCR demonstrated iNOS in approximately 70{\%} of bladders obstructed for 1 and 3 weeks, while the iNOS protein was apparent in 50{\%} of the bladders from the same groups. Conclusions: This new animal model of infravesical obstruction is reliable and reproducible. Moreover, the physiologic changes noted are comparable to other models, but an added advantage is the relevance of this model with regard to studying new transgenic or knockout mice. Enhanced expression of iNOS seen early after obstruction may serve to improve oxygenation during obstruction-induced ischemia.",
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