Volume-induced responses in the isolated bladder: evidence for excitatory and inhibitory elements

To quantify changes in autonomous activity in response to alterations in intravesical volume, to explore the possible underlying regulatory mechanisms.

Experiments were conducted using whole isolated bladders from six female guinea pigs (280-400 g). A cannula was inserted into the urethra to monitor intravesical pressure and the bladder was suspended in a heated chamber containing carboxygenated physiological solution at 33-36 degrees C. All drugs were added to the solution on the ablumenal bladder surface.

An increase in intravesical volume followed by a rapid reduction lead to a complex series of activity comprising of several distinct phases. After a volume increase there was an initial 'burst' of frequency which gradually declined to a 'steady state'. After a volume reduction there was a period of quiescence with spontaneous activity gradually returning to levels seen before the increase, termed the 'inhibitory phase'. The frequency of transient contractions, both immediately after a volume increase and at steady state, increased both with increasing intravesical volume and dose of arecaidine. The length of the inhibitory phase increased both with the duration and magnitude of volume increase. However, the inhibitory phase was not entirely dependent n the magnitude of volume change, as the inhibitory phase was shorter when the volume was not returned to baseline levels. Increasing doses of arecaidine shortened the inhibitory phase.

These observations suggest that the regulation of volume-induced spontaneous activity relies on complex excitatory and inhibitory inputs. The rapid burst of activity resulting from a rise in volume suggests the presence of a rapidly adapting mechanism. Rapid reduction in intravesical volume leads to a quiescent period, i.e. the inhibitory phase. This is related to both the duration of intravesical volume increase and its magnitude. However, similar volume changes are more effective when the volume is reduced back to baseline, as opposed to the bladder being incompletely emptied. Furthermore, the frequency of transient contractions remained constant once a steady state was reached, with no evidence of inhibition before volume reduction. This suggests that mechanisms involved in the generation of the inhibitory phase initiated during bladder filling require >30 s to have a significant effect, but depend on a reduction in volume to be triggered, with the response dependent on the volume reduced. The mechanisms involved in generating and modulating the inhibitory phase seem to be regulated by a strong cholinergic input but the exact nature of these mechanisms is unknown. The potential importance of these results in terms of the general physiology and pharmacology of the bladder is discussed.