Faculty Collaboration Database

OAB without an overactive bladder in the acute prostaglandin E2 rat model. Am J Physiol Renal Physiol 2017 Nov 01;313(5):F1169-F1177

Date

08/05/2017

Pubmed ID

28768666

Pubmed Central ID

PMC5792156

DOI

10.1152/ajprenal.00270.2017

Scopus ID

2-s2.0-85036501656 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

Intravesical prostaglandin E2 (PGE2) was previously used to induce overactive bladder (OAB) symptoms, as it reduces bladder capacity in rats and causes a "strong urgency sensation" in healthy women. However, the mechanism by which this occurs is unclear. To clarify how PGE2 reduces bladder capacity, 100 µM PGE2 was administered intravesically during open, single-fill cystometry with simultaneous measurement of sphincter EMG in the urethane-anesthetized female Wistar rat. PGE2 was also applied to the urethra or bladder selectively by use of a ligature at the bladder neck before (urethra) or during (bladder) closed-outlet, single-fill cystometry. Additional tests of urethral perfusion with PGE2 were made. PGE2 decreased bladder capacity, increased voiding efficiency, and increased sphincter EMG during open cystometry compared with saline controls. The number of nonvoiding contractions did not change with PGE2; however, bladder compliance decreased. During closed-outlet cystometry, PGE2 applied only to the bladder or the urethra did not decrease bladder capacity. Urethral infusion of PGE2 decreased urethral perfusion pressure. Taken together, these results suggest that intravesical PGE2 may decrease bladder capacity by targeting afferents in the proximal urethra. This may occur through urethral relaxation and decreased bladder compliance, both of which may increase activation of proximal urethra afferents from distension of the proximal urethra. This hypothesis stands in contrast to many hypotheses of urgency that focus on bladder dysfunction as the primary cause of OAB symptoms. Targeting the urethra, particularly urethral smooth muscle, may be a promising avenue for the design of drugs and devices to treat OAB.

Author List

Hokanson JA, Langdale CL, Sridhar A, Grill WM

Author

James A. Hokanson PhD Assistant Professor in the Biomedical Engineering department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Dinoprostone
Disease Models, Animal
Electromyography
Female
Muscle Contraction
Muscle, Smooth
Rats, Wistar
Urethra
Urinary Bladder
Urinary Bladder, Overactive
Urination
Urodynamics