The passive and active contractile properties of the neurogenic, underactive bladder.
OBJECTIVE
To characterize passive and active changes in detrusor activity in a highly compliant bladder.


METHODS
Bladders from adult female Sprague-Dawley rats were used 5 weeks after lower thoracic (T8) spinal cord transection or a sham-operation. Passive wall properties were assessed by pressure-volume relationships from whole bladders and the tensile response of bladder strips after a rapid (<0.5 s) stretch. Active properties were assessed from the frequency and amplitude of spontaneous contractions of bladder strips, and their response to the inotropic TRPV4 agonist GSK1016790A.


RESULTS
Passive bladder wall stiffness of SCT bladders was significantly reduced compared to that of the sham-operated control group (N = 6 and 8, respectively) and SCT bladder strips relaxed more quickly than those from sham-operated rats. The frequency of spontaneous contractions was reduced in SCT rats, and their amplitude, expressed as a ratio of bladder wall stiffness, was greater than in sham-operated rats. GSK1016790A (0.1 μM) significantly increased amplitude in strips from both sham-operated and SCT groups.


CONCLUSIONS
There is no evidence of contractile failure in a highly-compliant bladder. The observations of reduced passive bladder wall stiffness and an enhanced rate of stress relaxation lead to the conclusion that increased compliance is marked by altered matrix properties that dissipate muscle force, thereby generating low pressures. Contractile agonists may be effective for improving bladder function in detrusor underactivity.
Institute of Biosciences and Medicine, University of Surrey, Guildford, UK.
John S
JS
Young
Louise
L
Johnston
Camille
C
Soubrane
Karen D
KD
McCloskey
Gordon
G
McMurray
Rachel
R
Eccles
Christopher H
CH
Fry
D000818:Animals; D005260:Female; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology*; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D049990:Membrane Transport Modulators / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000601:surgery; D013119:Spinal Cord Injuries / Q000503:physiopathology; D013312:Stress, Physiological / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors; D001743:Urinary Bladder / Q000502:physiology*; D001750:Urinary Bladder, Neurogenic / Q000503:physiopathology*; D016055:Urinary Retention / Q000209:etiology / Q000503:physiopathology
D049990:Membrane Transport Modulators; C530602:N-(1-((4-(2-(((2,4-dichlorophenyl)sulfonyl)amino)-3-hydroxypropanoyl)-1-piperazinyl)carbonyl)-3-methylbutyl)-1-benzothiophene-2-carboxamide; D013449:Sulfonamides; D050916:TRPV Cation Channels; C486577:Trpv4 protein, rat; D007930:Leucine