Effects of resiniferatoxin desensitization of capsaicin-sensitive afferents on detrusor over-activity induced by intravesical capsaicin, acetic acid or ATP in conscious rats.
Recent studies have provided evidence for a major role of urothelially released ATP acting on a subpopulation of pelvic afferent nerves in mechano-afferent transduction in the bladder. We investigated whether desensitization of capsaicin-sensitive nerve fibres by systemic resiniferatoxin (RTX)-pretreatment can counteract the detrusor over-activity induced by intravesical capsaicin, acetic acid or ATP. Cystometric investigations were performed on awake female Sprague-Dawley rats before and 24 h after injection of RTX (0.3 mg/kg s.c.) or vehicle. The effects of intravesically instilled ATP (0.1 or 1.0 mM), capsaicin (30 microM) or acetic acid (pH 4.0) were compared with those of intravesical saline. RTX, but not its vehicle, significantly increased threshold pressure, voiding interval, micturition volume and bladder capacity. In the vehicle-pretreated rats, intravesical instillation of capsaicin or acetic acid significantly decreased voiding interval, micturition volume, and bladder capacity. However, in the RTX-pretreated rats, neither capsaicin nor acetic acid affected any parameter. On the other hand, intravesical ATP (0.1 mM) significantly decreased voiding interval and micturition volume in both groups of animals. At 1.0 mM, ATP also increased basal pressure and decreased the pressure threshold for micturition in both groups. The present results support the view that increased extracellular ATP has a role in mechano-afferent transduction in the rat bladder and that ATP-induced facilitation of the micturition reflex is mediated, at least partly, by nerves other than capsaicin-sensitive afferent nerves.
Zhang
Xiaoyang
X
Department of Urology, Shinshu University School of Medicine, 3-1-1 Asahi, 390-8621 Matsumoto, Japan.
Igawa
Yasuhiko
Y
Ishizuka
Osamu
O
Nishizawa
Osamu
O
Andersson
Karl-Erik
KE
D019342:Acetic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000283:Administration, Intravesical; D000344:Afferent Pathways / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004224:Diterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D007279:Injections, Subcutaneous; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology
D004224:Diterpenes; D004338:Drug Combinations; D000255:Adenosine Triphosphate; C024353:resiniferatoxin; D019342:Acetic Acid; D002211:Capsaicin