Pharmacological modulation of the spatiotemporal disposition of micromotions in the intact resting urinary bladder of the rabbit; their pattern is under both myogenic and autonomic control

Abstract

Objectives: To explore and characterize the disposition and dynamics of micromotions in the wall of the intact resting teradotoxinized urinary bladder of the rabbit before and after the administration of adrenergic and cholinergic pharmaceutical agents. Methods: Spatiotemporal maps and related intravesical pressure were used to analyse propagating patches of contractions (PPCs) and their component individual myogenic contractions [propagating individual contractions (PICs)] in the wall of the tetradotoxinized urinary bladder. Results: The bladder wall exhibited two contractile states that were of similar frequencies to those of the two types of electrophysiological discharge described in previous studies; the first, in which cyclic PPCs predominated, the second in which small irregular PICs predominated. The addition of carbachol increased the size, frequency, speed and distance of propagation of PPCs, whereas the addition of isoprenaline temporarily halted the incorporation of PICs into PPCs, and reduced patch size and total area undergoing contraction. The RhoA kinase (ROCK) inhibitor Y-27632 reduced both largest patch index and mean patch size. Both carbenoxolone and ROCK inhibition decreased the duration of PPCs. Carbenoxolone also prolonged duration and accelerated PPC propagation velocity. The authors postulate that these differences arise from differing effects of these agents on myocytes and interstitial cells within the stress environment of the bladder, influencing the development, coordination and propagation of PPCs. Conclusions: The timings and structure of spontaneous micromotions in the wall of the isolated bladder change when it is treated with sympathetic/parasympathetic agonists and with myogenically active agents. Correspondingly, disorders of bladder wall contraction may result from disorders of either neurogenic or myogenic signalling and may be amenable to treatment with combinations of agents that influence both.