Modulatory effects of intravesical P2X2/3 purinergic receptor inhibition on lower urinary tract electromyographic properties and voiding function of female rats with moderate or severe spinal cord injury.
BJU Int
; 123(3): 538-547, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30255543
ABSTRACT
OBJECTIVES:
To evaluate the role that intravesical P2X2/3 purinergic receptors (P2X2/3Rs) play in early and advanced neurogenic lower urinary tract (LUT) dysfunction after contusion spinal cord injury (SCI) in female rats. MATERIALS ANDMETHODS:
Female Sprague-Dawley rats received a thoracic Th8/Th9 spinal cord contusion with either force of 100 kDy (cN); moderate) or 150 kDy (cN; severe); Sham rats had no injury. Evaluations on urethane-anesthetised rats were conducted at either 2 or 4 weeks after SCI. LUT electrical signals and changes in bladder pressure were simultaneously recorded using cystometry and a set of custom-made flexible microelectrodes, before and after intravesical application of the P2X2/3R antagonist AF-353 (10 µM), to determine the contribution of P2X2/3R-mediated LUT modulation.RESULTS:
Severe SCI significantly increased bladder contraction frequency, and reduced both bladder pressure amplitude and intraluminal-pressure high-frequency oscillations (IPHFO). Intravesical P2X2/3R inhibition did not modify bladder pressure or IPHFO in the Sham and moderate-SCI rats, although did increase the intercontractile interval (ICI). At 2 weeks after SCI, the Sham and moderate-SCI rats had significant LUT electromyographic activity during voiding, with a noticeable reduction in LUT electrical signals seen at 4 weeks after SCI. Intravesical inhibition of P2X2/3R increased the ICI in the Sham and moderate-SCI rats at both time-points, but had no effect on rats with severe SCI. The external urethral sphincter (EUS) showed strong and P2X2/3R-independent electrical signals in the Sham and moderate-SCI rats in the early SCI stage. At 4 weeks after SCI, the responsiveness of the EUS was significantly attenuated, independently of SCI intensity.CONCLUSIONS:
This study shows that electrophysiological properties of the LUT are progressively impaired depending on SCI intensity and that intravesical P2X2/3R inhibition can attenuate electrical activity in the neurogenic LUT at early, but not at semi-chronic SCI. This translational study should be useful for planning clinical evaluations.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Éteres Fenílicos
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Pirimidinas
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Traumatismos da Medula Espinal
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Uretra
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Micção
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Bexiga Urinaria Neurogênica
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Antagonistas do Receptor Purinérgico P2X
Limite:
Animals
Idioma:
En
Revista:
BJU Int
Ano de publicação:
2019
Tipo de documento:
Article