Changes in bladder tone during filling: pharmacological aspects.

The mechanism by which the bladder maintains a low pressure during filling has not yet been established. Myogenic and neural factors have been suggested, although their relative importance has not been settled. There is an ongoing thoracolumbar sympathetic outflow to the lower urinary tract during filling, and noradrenaline, released from adrenergic nerves and acting through stimulation of beta-adrenoceptors (beta 2 and beta 3), may relax the bladder, due to a relative dominance of beta- over alpha-adrenoceptors in the detrusor. Non-adrenergic, non-cholinergic mediators, such as nitric oxide and vasoactive intestinal polypeptide have been suggested to relax the detrusor during filling; there is no compelling evidence to support these proposals. Unidentified relaxant factors may be released from the bladder. Their existence and possible importance need to be further documented. Although it is widely accepted that there is no sacral parasympathetic outflow to the bladder during filling, antimuscarinic drugs increase, and anticholinesterase inhibitors decrease bladder capacity, suggesting an ongoing acetylcholine (ACh) mediated stimulation of detrusor tone. If this is correct, agents inhibiting ACh release should be expected to contribute to bladder relaxation during filling. Inhibition of ACh release can be obtained by stimulation of various receptors on cholinergic nerves, including alpha 2-adrenoceptors, receptors for neuropeptide Y and galanin, or by antagonism of neuronal 5-HT4 receptors. Whether any of these mechanisms is of importance for bladder relaxation during filling, or whether they can be targets for pharmacological therapeutic interventions, remains to be established.