Volume-induced effects on the isolated bladder: a possible local reflex

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Abstract
To: (i) determine the effects of changing intravesical volume on autonomous activity in the isolated whole bladder of the guinea pig; (ii) identify the mechanisms which might contribute to induced changes; and (iii) explore the idea that changes in bladder volume which affect phasic activity are part of a local reflex operating within the bladder wall. Bladders were isolated from female guinea pigs, cannulated via the urethra and maintained in vitro in Tyrode's solution. The intravesical pressure (IVP) was monitored and drugs added to the bathing solution. The isolated unstimulated bladder containing 500-600 microL of fluid generates small (1-2 cm H2O) phasic rises in IVP, i.e. autonomous activity. When the bladder volume was increased, autonomous activity increased. In the presence of muscarinic agonists (100 nmol/L arecaidine and carbachol 100 nmol/L) autonomous activity is augmented, giving rise to large (>10 cm H2O) phasic rises in IVP. When the volume was increased, both the amplitude and frequency of the transients increased. When the bladder volume was reduced there was a period of marked inhibition of phasic activity. To explore the mechanisms underlying these changes the possible involvement of local neural reflexes was explored. The neurotoxin tetrodotoxin had no effect on the volume-induced changes. Sensory nerves are insensitive to tetrodotoxin and thus to assess their possible contribution bladders were exposed to capsaicin (10 micromol/L) to stimulate and eliminate sensory fibres; capsaicin caused complex changes in phasic activity, i.e. an initial increase, a secondary slowing and decrease, followed by a period of recovering amplitude and increased frequency. These changes suggest actions of the sensory nerves on the phasic mechanism indicative of a local axonal reflex. Once the phasic activity had returned to levels before capsaicin, changes in bladder volume still produced increases in activity and inhibition after the volume decrease. Interstitial cells (cells capable of increasing cGMP) are found in the bladder wall; to assess their possible role in the volume-induced changes, bladders were treated with 30 micromol/L ODQ, an inhibitor of guanyl cyclase, for 30-60 min. The volume-induced rise in frequency was little affected but the inhibition seen on volume reduction was reduced. These results show that there are components in the bladder wall which respond to distension by affecting phasic activity. This stimulus/response may reflect a volume 'reflex' within the bladder wall, consisting of excitatory and inhibitory components. This local reflex does not appear to involve directly motor or sensory nerves, although the latter can affect phasic activity, and their actions may represent a further reflex mechanism in the bladder wall. The possible involvement of guanyl cyclase in the volume-induced inhibition may indicate a role for interstitial cells. The physiological role of these mechanisms as a component of a motor/sensor system in the bladder wall is discussed.