Rat detrusor overactivity induced by chronic spinalization can be abolished by a transient receptor potential vanilloid 1 (TRPV1) antagonist.
OBJECTIVE
To evaluate the effect of a transient receptor potential vanilloid 1 (TRPV1) antagonist GRC 6211 on neurogenic detrusor overactivity (NDO) of spinal origin.


METHODS
Cystometries under urethane anaesthesia were obtained in 14 chronic spinalized rats to confirm NDO. Two groups were created. In the first one (n=10), GRC 6211 (0.01, 0.1 and 1mg/kg weight) was administered via the duodenum in cumulative doses and cystometries performed 150 min after the administration of each dose of the drug. In the second group (n=4), used as control, the animals were submitted to cystometries during 12 hours, without administration of GRC 6211. Frequency and amplitude of bladder contractions were recorded in both groups.


RESULTS
The mean (±SDev) bladder detrusor muscle contraction frequency of spinalized rats was 0.7±0.27 contractions/min. GRC 6211 produced a significant dose-dependent effect, with the frequency diminished to 0.53±0.23, 0.40±0.20 and 0.20±0.13 contractions/min, respectively. The mean (± SDev) amplitude of bladder contractions was 48.4±4.4 cmH(2)O. After administration of 0.01 mg/kg, 0.1mg/kg and 1mg/kg of GRC 6211, the amplitude decreased to 47.1±4.3, 45.6±5.6 and 40.2±4.1 cm H(2)O respectively. The effect was significant at 0.1 and 1mg/kg doses. Cystometries performed in the control group of spinalized rats showed no evidence of detrusor fatigue caused by the urethane anaesthesia and long duration of the experiment.


CONCLUSIONS
TRPV1 antagonists may be very effective in reducing NDO of spinal origin. This finding may have profound implications for the pathogenesis and future treatment options of patients with spinal NDO.
Department of Urology, Hospital de São João, Porto, Portugal.
André
A
Santos-Silva
Ana
A
Charrua
Célia D
CD
Cruz
Laxmikant
L
Gharat
António
A
Avelino
Francisco
F
Cruz
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000150:complications / Q000503:physiopathology*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D016896:Treatment Outcome; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology
C572329:GRC 6211; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014508:Urea