Agonist‐ and Nerve‐Induced Phasic Activity in the Isolated Whole Bladder of the Guinea Pig: Evidence for Two types of Bladder Activity

Abstract

Spontaneous localised propagating waves of contraction and localised stretches have been reported to occur in the isolated whole bladder of the guinea pig. The physiological role and the cellular processes underlying these events are unknown. In order to gain insight into the mechanisms generating this complex activity, experiments were performed to examine and compare the responses of the whole bladder preparation to (i) the muscarinic agonists carbachol and arecaidine, (ii) the nicotinic ligand lobeline and (iii) nerve stimulation. High concentrations of the muscarinic agonists (>3 μM) induced a slow rise in intra‐vesical pressure upon which were superimposed pressure transients, while low concentrations (< 300 nM) induced only phasic rises in pressure. One interpretation of these data is that there are two separate mechanisms activated by muscarinic agonists: one generating contracture and the other phasic activity. Immunocytochemical staining revealed M3 muscarinic receptors on smooth muscle cells within trabeculae and a second population of positive cells in the sub‐urothelial layer. This observation raises the possibility that the actions of muscarinic agonists are a consequence of activating different cell types. Lobeline (1‐60 μM) activated phasic contractions but did not cause a rise in basal pressure. Atropine did not inhibit the lobeline‐induced responses but abolished the muscarinic responses. Also, hexamethonium or tetrodotoxin did not affect the lobeline‐induced responses. These observations suggest that the mechanism generating phasic activity is activated by a nicotinic stimulus that does not involve ganglia, nerves or the neuromuscular junction. Stimulation of the bladder nerve at frequencies between 20 and 30 Hz for 5 s resulted in a rapid rise in intra‐vesical pressure. Prolonged nerve stimulation (10‐200 s) at frequencies between 1 and 10 Hz activated phasic rises in pressure. Low frequency nerve stimulation increased the frequency of agonist‐induced phasic activity. Thus, nerve stimulation can also produce two forms of activity and low frequency stimulation can augment the processes generating phasic activity. These observations suggest that there are two distinct types of bladder activity: global contractions involving most of the bladder wall and phasic contractions comprising propagating waves of contraction. The mechanisms generating these contractile events appear to be different and they may involve cells located in different regions of the bladder. The nature of these mechanisms and their possible physiological significance is discussed.

Comparison study of autonomous activity in bladders from normal and paraplegic rats

“…These ¢ndings are consistent with various reports of increased activity in overactive bladder structures [Brading, 1997]. Gillespie et al [2003] used the term ''castellation'' to describe the typical con¢guration of transients in normal guinea pig bladders. This castellation equals the localization of spikes on top of macro-transients, which we typically observed in healthy rat bladders; in neurogenic bladders this phenomenon seemed to be disturbed in di¡erent aspects.…”

“…Modulation of this activity has been demonstrated with diverse agents. Carbachol, areca «|dine (muscarinic agonists), lobeline (nicotinic agonist), a,bmethylene ATP (ATP-analogues), substance P and the nitric oxide donor sodium nitroprusside have all been shown to increase the frequency of autonomous transients [Gillespie et al, 2003;Gillespie and Drake, 2004;Gillespie, 2004a]. Atropine and tetrodoxin abolished the agonist-induced augmentation of activity; however they did not a¡ect the baseline activity [Gillespie, 2004a].…”

The Integrative Physiology of the Bladder

“…Once the bladder has been distended slightly, or exposed to a low concentration of a muscarinic acetylcholine agonist, bladder wall movements take the form of waves of contraction propagating over varying distances across the bladder surface. 11 2. Exaggerated, co-ordinated bladder wall movements should be apparent in DO; the co-ordinated activity in a substantial proportion of the bladder wall will predictably result in more considerable effects on the intravesical pressure.…”

“…Accordingly, lesions at several levels of the central and peripheral nervous system can have similar effects on lower urinary tract function. 11 During the voiding phase, the myovesical plexus sustains detrusor contraction so long as the comparator tells it this is necessary, i.e. up until completion of bladder emptying.…”

Selective reversal of muscle relaxation in general anesthesia: focus on sugammadex

“…60,65,69 When administered to volunteers who had not received a neuromuscular blocking agent, doses of 0.1-8.0 mg/kg of sugammadex had a clearance rate of 88 mL/minute, an elimination half-life of 1.8 hours, and a volume of distribution of 11-14 L. 65,70 Approximately 75% of the dose was eliminated renally. Between 59% and 80% of the sugammadex dose is excreted renally in the first 24 hours after administration.…”