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Author(s): Santos-Silva, A.
Charrua, Ana
Cruz, C.D.
Gharat, L.
Avelino, A.
Cruz, F.
Title: Rat detrusor overactivity induced by chronic spinalization can be abolished by a transient receptor potential vanilloid 1 (TRPV1) antagonist
Issue Date: 2012
Abstract: Purpose: To evaluate the effect of a transient receptor potential vanilloid 1 (TRPV1) antagonist GRC 6211 on neurogenic detrusor overactivity (NDO) of spinal origin. Materials and 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 1 mg/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, 0.1 mg/kg and 1 mg/kg of GRC 6211, the amplitude decreased to 47.1 +/- 4.3, 45.6 +/- 5.6 and 40.2 +/- 4.1 cmH(2)O respectively. The effect was significant at 0.1 and 1 mg/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. Conclusion: 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. (C) 2011 Elsevier B.V. All rights reserved.
Subject: Ciências da Saúde, Ciências médicas e da saúde
Health sciences, Medical and Health sciences
Scientific areas: Ciências médicas e da saúde
Medical and Health sciences
Document Type: Artigo em Revista Científica Internacional
Rights: restrictedAccess
Appears in Collections:FCNAUP - Artigo em Revista Científica Internacional

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