In vivo motor effects of loperamide on the rat urinary bladder

Bladder motility recordings were performed in anaesthetized rats and the effect of the peripherally active opiate agonist loperamide on urinary bladder function was studied. Regional intra-arterial administration of loperamide (0.01–2 mg kg^-1) induced weak bladder contraction per se. Loperamide caused an effective dose-dependent inhibition of bladder motility induced by regional injection of the receptor agonists acetylcholine (ACh) and substance P (SP), as well as by peripheral motor nerve stimulation (PNS). Pretreatment with naloxone (0.5 mg kg^-1) partially antagonized the inhibitory action of loperamide on the nerve-mediated detrusor contraction. However, the depression of the motor responses induced by the receptor agonists ACh and SP was not influenced. It is suggested that the demonstrated inhibitory effect of loperamide on bladder motility is partially mediated by peripheral opioid receptors. The main non-opioid part of the inhibition might be a direct smooth muscle action.     

In vivo motor effects of loperamide on the rat urinary bladder.

Bladder motility recordings were performed in anaesthetized rats and the effect of the peripherally active opiate agonist loperamide on urinary bladder function was studied. Regional intra-arterial administration of loperamide (0.01-2 mg kg-1) induced weak bladder contraction per se. Loperamide caused an effective dose-dependent inhibition of bladder motility induced by regional injection of the receptor agonists acetylcholine (ACh) and substance P (SP), as well as by peripheral motor nerve stimulation (PNS). Pretreatment with naloxone (0.5 mg kg-1) partially antagonized the inhibitory action of loperamide on the nerve-mediated detrusor contraction. However, the depression of the motor responses induced by the receptor agonists ACh and SP was not influenced. It is suggested that the demonstrated inhibitory effect of loperamide on bladder motility is partially mediated by peripheral opioid receptors. The main non-opioid part of the inhibition might be a direct smooth muscle action.     

The motor innervation of the rat urinary bladder

1. The post-ganglionic nerves visible in silver-impregnated sections of a normal rat bladder were absent 14 days after both pelvic ganglia had been ablated. After ablation of one ganglion the distribution of nerve trunks in either side of the organ was unchanged. Post-ganglionic axons from either side appear to distribute bilaterally.2. The acetylcholine (ACh) content of the rat bladder was reduced from control by 50% after the post-ganglionic nerves from one ganglion had degenerated. However, the ACh content in the two halves of the bladder sectioned along the mid line was the same after one nerve had degenerated.3. Motor responses of bladder preparations elicited during stimulation of both pelvic nerves were compared with responses elicited when each nerve was stimulated separately. In three-quarters of the animals the sum of the individual responses exceeded the response to combined nerve stimulation by no more than 20%. The functional overlap between the two groups of motor nerves to the bladder was therefore no greater than this amount in most animals.4. Motor responses of normally innervated bladder preparations elicited in vitro by transmural stimulation were compared with responses elicited after the post-ganglionic innervation from one side had degenerated. The mean response of bladders with half their innervation was 50-65% of the mean response of bladders normally innervated. The functional overlap by the two groups of nerves was found to be no greater than 15%.     

Central nervous system neurons labelled following the injection of pseudorabies virus into the rat urinary bladder.

Pseudorabies virus was injected into the wall of the urinary bladder and, following incubation times of 2, 3 and 4 days, central nervous tissue was processed immunohistochemically for the presence of virus. Longer incubation times resulted in more extensive spread of the virus. Infected neurons were initially found in the spinal cord (mainly lumbosacral) and, after longer survival times, in raphe nuclei, reticular area, pontine micturition center, locus coeruleus, red nucleus, hypothalamus, preoptic, and cortical areas. These data define a multisynaptic circuit of neurons whose ultimate output influences urinary bladder function.     

Transient supersensitivity in the hypertrophied rat urinary bladder

The presence of a paraffin bolus intravesically for 1 or 4 weeks was accompanied by an approximate three-fold increase in bladder weight. A supersensitivity to methacholine was demonstrated in these hypertrophied bladders at 1 week but not at 4 weeks. At the earlier time of observation, the contractile responses in vitro to nerve stimulation were reduced, while at the later time of observation the responses were the same as those of controls; the atropine-sensitive fraction of the response was entirely responsible for the recovery. The concentration of choline acetyltransferase, indicating cholinergic nerve density and initially reduced by about 50%, rose in course of time. It is suggested that in the beginning of the experimental period, the muscle cells of the hypertrophied bladders in situ are exposed to 'subnormal' transmitter concentration. An extension of the field of innervation of the cholinergic nerves may explain the disappearance of the supersensitivity.     

Reversible papillary hyperplasia of the rat urinary bladder.

A rapid reproducible method for the production of ulcers and reversible regenerative hyperplasia of the urinary bladder of rats is described. This method does not involve administration of a toxic chemical or retention of a foreign body. Ulceration was produced by means of applying a steel rod, 5 mm in diameter, frozen at -78 C, to the serosal surface of the bladder for 2 seconds, twice, with a 5-second interval between each application. Sequential histologic observations showed that ulcers were accompanied by necrosis of the entire thickness of the bladder at the site of freezing with extensive acute inflammation. Regenerative hyperplasia was evident at the edge of the ulcer by the second day, with greatest severity at 5 days when papillary and nodular hyperplasia were present. At 15 days the bladders were normal or had only minimal hyperplasia. The labeling index by autoradiography was highest in the mildly hyperplastic area near the ulcer at 2 days and remained relatively high through 5 days. The hyperplastic epithelium surrounding the ulcer observed by scanning electron microscopy had numerous degenerative cells on the surface, and small epithelial cells with numerous short, uniform microvilli on their luminal surface were also observed. The numerous short, uniform microvilli on their luminal surface were also observed. The microvilli had a symmetric luminal membrane, as observed on trasmission electron microscopy. More peripherally the cells had microridges only or microvilli and microridges on their luminal surface. Neither pleomorphic microvili nor a structured glycocalyx fuzz on microvilli was observed during the process of regenerative hyperplasia, distinguishing it from neoplastic bladder proliferations.     

Morphological analysis of the acute effects of overdistension on the extracellular matrix of the rat urinary bladder wall.

PURPOSE: To investigate the morphological effects of acute overdistension in the structure of the extracellular matrix of the bladder wall in rats. MATERIALS AND METHODS: The bladders of a group of 6 male Wistar rats were transurethrally overdistended for 3 hours. Another identical group (the control group) was only submitted to a sham operation. Specimens from the bladder dome were analyzed with light microscopy (LM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). RESULTS: LM--The control group bladders had a 4 to 5 layer urothelium, a lamina propria, and a smooth muscle layer with longitudinal and transversal fibers. The overdistended bladders presented an intense interstitial infiltrate in the lamina propria, and a less intense infiltrate among the smooth muscle fibers. TEM--The cells of the overdistended bladders had a significant amount of vacuoles, unlike the control bladders, where such vacuoles were scarce or absent. SEM--A delicate three-dimensional mesh of collagen fibrils was observed in the lamina propria of the bladder walls from the control group. Whilst for the control group this mesh consisted of distinct geometric structures, with mostly circular cellular spaces surrounded by the fibrils, the overdistended group showed evidence of distortion of the mesh, with flattened and elongated cellular spaces. CONCLUSIONS: Acute bladder overdistension induces structural modifications, altering the arrangement and interaction of collagen fibrils, as well as incipient tissue damage as edema in the lamina propria and smooth muscle layers.     

Age-dependence of the spontaneous activity of the rat urinary bladder

Abnormal mechanical function of the bladder is manifested in a number of ways including higher frequency of involuntary detrusor contractions associated with reduced compliance of the bladder that is responsible for an increase in intraluminal pressure during filling. There are basically two ways to approach experimentally these problems: (1) by studying the neural control of the lower urinary tract function, and (2) by measuring the properties of smooth muscle cells in the bladder wall. Studies on smooth muscle function often do not take the origin of smooth muscle cells into account i.e., whether they were harvested from normal or overactive bladders. Although, this simplistic view may be beneficial to understanding the generation of the spontaneous activity of the bladder, however, it does not sufficiently explain the cell-to-cell propagation of the spontaneous smooth muscle activity. The spontaneous activity of smooth muscle is an important factor that works against the bladder compliance in the filling phase, and may inversely affect the neurally evoked response during micturition. The intensity of spontaneous activity is the age-dependent; it is high in neonatal bladders it is small or almost non-existent in adults and reemerges in older bladders. This review focuses on these age-dependent alterations of spontaneous bladder contractions and describes the possible mechanisms which may have important role in regulating the spontaneous contractions using the rat as an animal model.     

Hyperplasia and hypertrophia in the denervated and distended rat urinary bladder

The parasympathetically denervated and distended rat urinary bladder was found to have increased fourfold in weight when examined 3 weeks postoperatively. Both in muscularis and mucosa of such a bladder the synthesis of proteins, RNA and DNA was increased severalfold. An increase in the polyamines putrescine, spermidine and spermine was also found; these polyamines are usually linked to protein synthesis. The results suggest that the cells of the two layers increase both in size and number. Hyperplasia was, in a previous study, suggested as a possible explanation for a right-ward shift of the active length-tension curve of muscle strips in the denervated rat urinary bladder.     

Disuse as cause of supersensitivity in the rat urinary bladder

Ureterostomia in situ was performed to reduce the nervous reflex activation of the bladders without concomitant hypertrophy. In muscle strips of these disused and non-hypertrophied bladders, supersensitivity to methacholine was demonstrated, which did not increase between 1 and 3 weeks. The supersensitivity did not increase further by combining urinary diversion with section of the preganglionic bladder nerves (decentralization). From the present results it may be concluded that in decentralized and hypertrophied bladders not only hypertrophy per se, previously studied (Ekstr?m et al. 1985), but also loss of nerve impulse traffic (cf. urinary diversion) contribute to the development of supersensitivity.