Beta3-Adrenoceptors in the Rat Sacral Spinal Cord and Their Functional Relevance in Micturition Under Normal Conditions and in a Model of Partial Urethral Obstruction

Abstract

Aims: Beta3-adrenoceptor selective agonists are evaluated as a new treatment for patients with lower urinary tract symptoms. It is believed that beta 3-AR selective agonists exert their effects via a peripheral site of action. However, beta 3-ARs have been found in brain tissue. This study examined whether beta 3-ARs are present in rat sacral spinal cord, and whether there are differences in beta 3-AR expression between normal and partial urethral obstruction (PUO) animals, and furthermore assessed the functional relevance of spinal beta 3-ARs for micturition. Methods: Thirty-eight male Sprague-Dawley rats underwent either PUO or sham-operation. Two weeks after operation, half of the animals were used for histomorphological analysis. Remaining animals were used for functional experiments, where a beta 3-AR selective agonist, BRL 37344, was given intrathecally. Bladder function was assessed by continuous cystometry in non-anesthetized animals before and after drug administration. Results: Beta3-ARs were found in sacral spinal cord segments with an accumulation in the ventral horn. There was a significant increase of beta 3-AR expression in obstructed rats. in functional experiments obstructed rats showed increased bladder weight, micturition frequency, spontaneous activity, and bladder pressures (all P < 0.05) compared to controls. Intrathecally administered BRL 37344 showed no effect in non-obstructed rats. in obstructed rats intrathecal BRL 37344 significantly reduced bladder pressures, spontaneous activity, and micturition frequency (all P < 0.05). Conclusions: Beta3-ARs are present in rat sacral spinal cord, and are significantly up-regulated after PUO. Besides their well-established peripheral site of action in the treatment of voiding dysfunction, beta 3-AR selective agonists might exert relevant effects at a central nervous site of action. Neurourol. Urodynam. 30:1382-1387, 2011. (C) 2011 Wiley-Liss, Inc.