Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, PC45

Poster Communications

Contribution of central and peripheral mechanisms for non-micturition contractions in rat bladder function

P. Sadananda1, M. J. Drake2, J. F. Paton1, A. E. Pickering1

1. University of Bristol, Bristol, United Kingdom. 2. Bristol Urological Institute, Bristol, United Kingdom.


Using a novel decerebrate arterially perfused preparation of the whole rat, the micturition reflex was evoked by fluid infusion into the bladder and non-micturition contractions (NMCs) were characterised. Female Wistar rats (40-80g) were anaesthetized with 2-4% halothane. The bladder was accessed via a laparotomy. The stomach, spleen and intestine were tied and removed. The animal was immersed in cold artificial CSF and decerebrated, at which point anesthesia was withdrawn. The preparation was perfused with carbogenated aCSF (32C) via a double lumen cannula inserted into the aorta. The heart resumed beating and rhythmic respiratory muscle contractions began within minutes, as perfusion pressure reached 70mmHg. A suction electrode recorded phrenic nerve activity. A cannula, connected to a 3-way tap was inserted into the bladder for filling and pressure monitoring. A bipolar suction electrode recorded external urethral sphincter (EUS) EMG. A second bipolar electrode measured pelvic bladder afferent nerve activity. All preparations showed characteristic rat filling and voiding responses lasting for 4 hours. NMCs were observed during basal conditions, with frequency and amplitude of 1.4±0.9/min and 3.6±0.5mmHg, respectively, and a duration of 10.9±0.7s (n=12). NMCs followed waves of peristaltic contractions that extended down the length of the ureters as fluid was passed from the kidneys. During slow rates of bladder distension (infusions <20µl/min), NMC frequency was higher as compared to fast infusion rates (infusions >80µl/min). Systemic application of M1 antagonist, pirenzipine abolished NMCs (n=2), although normal voiding responses remained, indicating the contribution of urothelial muscarinic receptors in NMC generation. Application of muscle relaxant, vecuronium bromide (2µg/ml) on EUS the decreased the amplitude of NMCs, resulting in leakage of urine likely due to lack of resistance. NMCs triggered bursts of discharge on the pelvic afferent nerve. Nociceptive c-fibre stimulation (with intravesical capsaicin) caused large amplitude NMCs (14.5±0.8 mmHg compared with paired control 2.3±0.4mmHg; P=0.0001; t-test) and associated tonic EUS firing. Subsequently, NMC and EUS activity decreased, as a result of desensitisation. Ganglion blockade by hexamethonium (330µM) increased NMC amplitude (but not frequency) by 86%, suggesting tonic inhibition by higher centers. Moreover, when brainstem control had deteriorated NMC amplitude (but not frequency) also increased (5.8±0.4 mmHg; P<0.0001). These results confirm that NMCs appear to be locally generated via mediator release from urothelial cells. They may serve as an assessment reflex during bladder distension relaying bladder fullness levels to higher centres. However, NMCs are modulated by the CNS which may prevent them from triggering a void until a volume threshold is reached.

Where applicable, experiments conform with Society ethical requirements