Effects of kinin B1and B2receptor antagonists on overactive urinary bladder syndrome induced by spinal cord injury in rats
| Autor: | Alessandra C. Martini, João B. Calixto, Rodrigo Medeiros, Stefânia Forner, Janice Koepp, Edinéia L. Andrade, Allisson Freire Bento |
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| Rok vydání: | 2012 |
| Předmět: |
Pharmacology
Detrusor muscle medicine.medical_specialty Urinary bladder medicine.diagnostic_test business.industry Urinary system Urology Cystometry Kinin urologic and male genital diseases medicine.disease female genital diseases and pregnancy complications medicine.anatomical_structure Overactive bladder medicine Urothelium business Spinal cord injury |
| Zdroj: | British Journal of Pharmacology. 167:1737-1752 |
| ISSN: | 0007-1188 |
| DOI: | 10.1111/j.1476-5381.2012.02127.x |
| Popis: | Background and Purpose Kinin B1 and B2 receptors have been implicated in physiological and pathological conditions of the urinary bladder. However, their role in overactive urinary bladder (OAB) syndrome following spinal cord injury (SCI) remains elusive. Experimental Approach We investigated the role of kinin B1 and B2 receptors in OAB after SCI in rats. Key Results SCI was associated with a marked inflammatory response and functional changes in the urinary bladder. SCI resulted in an up-regulation of B1 receptor mRNA in the urinary bladder, dorsal root ganglion and spinal cord, as well as in B1 protein in the urinary bladder and B1 and B2 receptor protein in spinal cord. Interestingly, both B1 and B2 protein expression were similarly distributed in detrusor muscle and urothelium of animals with SCI. In vitro stimulation of urinary bladder with the selective B1 or B2 agonist elicited a higher concentration-response curve in the SCI urinary bladder than in naive or sham urinary bladders. Cystometry revealed that treatment of SCI animals with the B2 selective antagonist icatibant reduced the amplitude and number of non-voiding contractions (NVCs). The B1 antagonist des-Arg9-[Leu8]-bradykinin reduced the number of NVCs while the non-peptide B1 antagonist SSR240612 reduced the number of NVCs, the urinary bladder capacity and increased the voiding efficiency and voided volume. Conclusions and Implications Taken together, these data show the important roles of B1 and B2 receptors in OAB following SCI in rats and suggest that blockade of these receptors could be a potential therapeutic target for controlling OAB. |
| Databáze: | OpenAIRE |
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