Pharmacology of ureter.

Ureter which performs the important function of transport of urine from kidney to the bladder is not a passive tube, but exhibits characteristic spontaneous (peristaltic) activity. This peristaltic activity is characterized by coordinated muscular contractions, which after originating from a spontaneously active primary pacemaker, situated in the vicinity of the pelvi ureteric junction, propagate downwards along the entire length of the ureter. In addition, the ureter, like the heart, possesses certain cells which become activated when the primary pacemaker is suppressed or there is an interruption of conduction, thereby, acting as latent pacemakers. (1) The peristaltic activity of the ureter is modified by several pharmacologically active substances. Moreover, some of these substances are occasionally able to initiate spontaneous activity even in quiescent ureters. This article briefly reviews the effects of catecholamines (adrenaline, noradrenaline and isoprenaline) and acetylcholine on the ureters of human beings and some domestic and laboratory animals.     

Autonomy of spontaneous rhythmogenesis of perivesicular area of cat ureter

The work presents data indicating no dependence of the pacemaker activity located in the zone of junction of cat ureter with urinary bladder on genesis of the main perirenal pacemaker. Data are presented on effect of clamping the renal artery supplying with blood flow the renal area on rhythmogenesis of the ureter perivesicular area. An inhibition of the pacemaker activity of the pyeloureteral anastomosis is observed. At the same time, no marked effect on automatism of the low organ area is revealed. Data of morphological studies of the vascular bed providing blood supply of various ureter areas are presented.     

Resting membrane potentials of pacemaker and non pacemaker areas in rat uterus

Microelectrode studies of pacemaker and non pacemaker cells in pregnant rat uterus have shown the pacemaker areas to have a constant value of RMP throughout pregnancy which was always significantly smaller than that of non pacemaker cells. The development of new pacemaker areas was associated with membrane depolarization. A number of agents and conditions which caused membrane depolarization also induced pacemaker activity in previously non pacemaker areas but did so at different levels of membrane depolarization. Potassium depolarization failed to induce pacemaker activity. It is concluded that a low level of RMP is an important factor but not sufficient alone to explain the occurence of pacemaker activity.The resting membrane potentials (RMP) of spontaneously active smooth muscles are appreciably smaller than those of nonspontaneously active muscles (3) and comparable in magnitude to those of other tissues showing spontaneous activity such as the frog sinus venosus(7), rabbit sino-auricular node (10) and embryonic heart muscle (6). In intestinal smooth muscle, where all cells appear to be spontaneously active, a clear relationship can be demonstrated between fluctuating levels of RMP and the incidence of action potential activity, and the ionic and metabolic basis of slow wave activity has been extensively investigated (5, 8). In other smooth muscles, such as the ureter and uterus, where electrical activity arises from pacemaker areas (11, 12), the underlying causes of spontaneous activity are less well understood and the relationships between pacemaker activity, RMP and excitability have not been clearly defined. As an initial approach to studying this problem we have chosen to investigate the relationship between RMP and pacemaker activity in the uterus of the pregnant rat.     

Effect of nifedipine on electrophysiological properties of rat ureter spontaneous activity

The work deals with effect of various concentrations of nifedipine on the slow and fast spontaneous activities evoked in the perivesical and perirenal areas of the rat ureter. Whereas in the proximal zone of the organ at the low dose of nifedipine (0.06 and 0.12 mg/kg), inhibition is revealed both of slow waves and of their corresponding spikes, in the perivesical part the opposite effect is observed. Besides, with further increase of the nifedipine dose to 0.15 and 0.2 mg/kg, in the ureter area adjacent to the urinary bladder, alongside with acceleration of slow pacemaker oscillations, the appearance of the antiperistaltically directed action potentials is also possible.     

Bioelectric activity of various parts of the upper urinary tract

Experiments on 50 dogs carried out by the method of in vivo electromyography have confirmed the localization of the pacemaker of the pyeloureter in the proximal end of the renal pelvis at the pelvicalyceal border. It is determined that the pacemaker biopotentials are characterized by higher frequency, low-voltage rhythmic amplitude, special form and the highest stability of parameters to the diuresis changes and adrenalin influence. Biopotentials are spreading in the distal direction with an increasing speed, amplitude and decreasing frequency. Pyeloureteral junction is the main rhythmoregulator of the bioelectric activity of the ureter. Synchronization of the bioelectric activity of different parts of the pyeloureter depends on the level of its excitability.     

Characterization of spontaneous electrical activity of the urinary tract: Ureter,bladder, urethra

The study aimed to characterize spontaneous electrical activity of the ureter, urinary bladder and urethra as well as their interrelationship. The basic parameters of pacemaker activity (amplitude, frequency, peak rise rate, peak rise time, peak half-width) were comparatively analyzed in each of the active areas. Out of the three areas compared, the ureteral rhythmogenic zone displayed the maximum amplitude and apex formation rate. Under conditions of urine influx from the ureter into the bladder and isolation of these organs from the urethra, the amplitude and peak rise rate in the latter decreased by almost 20%. At the same time, all the parameters of the ureter and bladder remained intact. Complete block of urine influx into the bladder by transecting the ureter at the appropriate area led to a slight decrease in the amplitude of action potentials, peak rise rate and rhythmogenicity frequency in the bladder, respectively, by 14.2, 12.5 and 16% at the constancy of other parameters of its activity. Subsequent isolation of the bladder from the urethra had no appreciable effect on the altered parameters of the former. The similar tendency towards a reduction of the parameters was observed under the same conditions in the urethra. Thus, a relationship was revealed between autonomous activities of the ureter, bladder and urethra. The regulatory role in this process is provided by the urine flow through these organs.     

Interstitial cell of Cajal-like cells in the upper urinary tract

Autorhythmicity in the upper urinary tract (UUT) has long been considered to arise in specialized atypical smooth muscle cells (SMC) predominately situated in the most proximal regions of the pyeloureteric system. These atypical SMC pacemakers have been thought to trigger adjacent electrically-quiescent typical SMC to fire action potentials which allow an influx of Ca2+ and the generation of muscle contraction. More recently, the presence of cells with many of the morphological, electrical and immunohistochemical characteristics of interstitial cells of Cajal (ICC), the pacemaker cells of the gastrointestinal tract, have been located in many regions of both the upper and lower urinary tract. This article reviews the evidence from the literature and from our laboratory supporting a role of both atypical SMC and ICC-like cells in the initiation and propagation of pyeloureteric peristalsis in the UUT. We propose a new model in which there are 2 populations of pacemaker cells, high frequency atypical SMC and lower frequency ICC-like cells, both of which can drive electrically-quiescent typical SMC. The relative presence of these 2 populations of pacemaker cells and the relatively-long refractoriness of typical SMC determines the decreasing frequency of contraction with distance from the renal fornix. In the absence of the proximal pacemaker drive from atypical SMC after pyeloureteral/ureteral obstruction or surgery, ICC-like cell pacemaking provides a compensatory mechanism allowing the ureter to maintain rudimentary peristaltic waves and movement of urine from the pyelon towards the bladder.     

Dual effects of dopamine on the adult heart of the isopod crustacean Ligia exotica

In the adult heart of the isopod crustacean Ligia exotica, the cardiac ganglion acts as the primary pacemaker with the myocardium having a latent pacemaker property. We show several lines of evidence that dopamine modulates the heartbeat of adult L. exotica affecting both pacemaker sites in the heart. Dopamine caused positive chronotropic (frequency increase) and inotropic (amplitude increase) effects on the heartbeat in a concentration dependent manner. The time courses of these effects were considerably different and the inotropic effect appeared later and lasted longer than the chronotropic effect. Dopamine rapidly increased the frequency of the bursting activity in the cardiac ganglion neurons and each impulse burst of the cardiac ganglion was always followed by a heartbeat. Moreover, dopamine slowly increased the amplitude and duration of the action potential plateau (plateau potential) of the myocardium. When the myocardial pacemaker activity was induced by application of tetrodotoxin, which suppresses cardiac ganglion activity, dopamine slowly increased the amplitude and duration of the myocardial plateau potential while decreasing its frequency. These results suggest that dopamine modulates the heartbeat in adult L. exotica producing a dual effect on the two pacemaker sites in the heart, the cardiac ganglion and myocardium.     

Further observations on upper urinary tract smooth muscle

Summary Light and electron microscopic techniques have been employed to study the arrangement and distribution of two types of muscle in the upper urinary tract of the rat. An outer layer of cells has been identified in the wall of the renal calix and pelvis. These cells are separated by connective tissue but possess numerous processes which make close contacts with adjacent cells. A layer of similar cells has not been observed in the wall of the upper ureter. The inner layer of muscle in the calix and pelvis is composed of larger cells similar to and apparently continuous with ureteric muscle. These cells are closely related to one another without intervening connective tissue and possess numerous bundles of myofilaments which extend along the length of the cell. The two types of muscle are closely related and, in the junctional region, cells of the outer layer are arranged along the length and make close contacts with one or more of the inner smooth muscle cells. A quantitative estimation has been made of nerve bundles associated with smooth muscle forming the outer layer of the calix and pelvis and with the muscle of the ureter. The results have shown a five fold increase in nerves associated with the caliceal muscle when compared with the ureter. The results are discussed in relation to the concept of a ureteric pacemaker.The authors wish to thank Professor G. A. G. Mitchell for his useful advice and encouragement.     

Multiplicity of pacemaker zones in Helix pomatia neurons

Intracellular microelectrode recordings from neurons ofHelix pomatia revealed several local zones of action potential generation both on the soma and on some of the branches of the neurons. Under certain conditions the activity of individual loci of the neuron membrane was synchronized to produce a normal action potential. It is suggested that the somatic membrane of neurons is heterogeneous in structure and consists of separate loci of an electrically excitable membrane, incorporating active and latent pacemaker zones. Neurons ofH. pomatia are characterized by two types of action potential with different triggering mechanisms: one (synaptic) type is generated under the influence of the EPSP, the other (pacemaker) arises through activation of endogenous factors for the neuron (pacemaker potentials). The interaction between synaptic and pacemaker potentials during integrative activity of the neuron is discussed.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 5, No. 1, pp. 88–94, January–February, 1973.     

Modeling of the influence of gap-junction coupling on synchronization of central and peripheral sinoatrial node cells

Mathematical modeling of the electric activity of pairs of true (central) and latent (peripheral) sinoatrial pacemaker cells coupled through gap junctions revealed that attenuation of coupling conductance increases the beat phase shift; below a critical conductance there is no synchronization. The phase difference also depends on the type of interacting cells, being maximal for a “central”-“peripheral” cell pair.     

The effects of noradrenaline, applied by microelectrophoresis on different cells of the rabbit's atrial pacemaker

Noradrenaline has been applied by microelectrophoresis to a small portion of the atrial pacemaker area in the rabbit's heart in order to study the local effects of this chemical transmitter separately from the ones deriving from other parts of the pacemaker area. In a first group of cells, whose action potential and location assimilate them to true pacemaker cells, noradrenaline caused a reduction in cycle length and an increase in the steepness of slow diastolic depolarization. In a second group of cells similar to latent pacemaker cells, noradrenaline caused no change in cycle length, the outstanding effect being an increase in the steepness of the slow diastolic depolarization which afterwards changed into a subthreshold oscillation. A third type of cells showed intermediate characteristics between the two previous groups. These results suggest that: a) the chronotropic effect of noradrenaline on the heart atrial pacemaker seems to be due to changes in the steepness of slow diastolic depolarization which can assume, in some instances, the shape of subthreshold oscillations; the effects on the other parameters in our preparation seem to be either less constant or less significant; b) the different effects which are obtained on various kinds of cells seem to be the result of a different degree of sensitivity to noradrenaline and to the more or less premature activation of mechanisms antagonizing the action of noradrenaline. The results are discussed on the basis of a model of spontaneous atrial pacemaking which has been recently proposed.     

Entrainment of a bursting neuron--II. Atypical cases

Entrainment to external rhythms was analyzed in atypical RPA-1 neurons of Helix pomatia L. stimulated orthodromically. Neurons with long-lasting bursts were tested only with supraharmonic frequencies. All cycle-stimulus relations described for typical oscillators did occur, with particularities due to the frequency of stimulation and the strong fluctuations of cycle parameters. Activity in pairs or triplets was refractory to entrainment. Instead, rhythmical pulses may transform the bimodal activity into a monomodal one. Continuously active neurons and silent ones were also tested. Fragmentation into bursts and long-period bimodal activity could be evoked respectively, suggesting the presence of a latent bimodal pacemaker behind these activities.     

Influence of sympathetic innervation on the membrane electrical properties of neonatal rat cardiomyocytes in culture

Co-cultures of rat ventricular myocytes and sympathetic neurons were established. Superior cervical ganglia and ventricles from newborn rats were enzymatically dissociated and plated in a culture dish. Experiments were done between the 3rd (when evidence of neuron-myocyte proximity arises) and the 5th day in culture (before the myocytes become confluent). Simultaneous intracellular recording from a cardiomyocyte and an attached neuron was done using conventional microelectrode techniques (resistance of 60-100 Mohm). The myocytes in co-culture were either quiescent or spontaneously contracting. The contracting cells were either latent pacemaker or ventricular-like myocytes. The action potential (AP) characteristics of cardiomyocytes in co-cultures were comparable to those recorded in cardiomyocytes in pure cultures. Sympathetic innervation of the cardiomyocytes in co-cultures was evidenced by stimulating the neuron and observing an increase in rate of beating in latent pacemaker myocytes (average increase of 19.4 +/- 4.6%). In quiescent cardiomyocytes, neural stimulation evoked a slow depolarization that can reach threshold and initiate APs in the cell. This response is similar to slow excitatory postsynaptic potentials (EPSPs) observed in other synapses. Slow ESPSs could also be recorded in spontaneous beating cells, made quiescent by nifedipine (1x10(-6)-1x10(-7) M). These results indicate that functional synaptic contacts are developed in co-culture of sympathetic neurons and cardiac myocytes, and slow EPSPs can be evoked in cardiomyocytes as well as in other excitable cells. The sympathetic innervation occurring in culture did not significantly modify the spontaneous AP characteristics of the cardiomyocytes.     

Abnormalities in ureter and kidney development in mice given acetazolamide-amiloride or dimethadione (DMO) during embryogenesis.

These experiments more accurately define the effects of the combination acetazolamide-amiloride or a single dose of dimethadione (DMO), the active metabolite of trimethadione, on the development of the ureter. When acetazolamide-amiloride was administered in C57BL/6NCrlBR mice on day 9, 9.5, or 10 of gestation (plug = day 0) a second ureter was formed, anterior to the original ureter, inducing a second kidney. The second ureter then fails to make a connection with the developing bladder and remains attached to the mesonephric duct. The mesonephric duct becomes the vas deferens in the male and deteriorates completely in the female leading to either a restricted ureter or a blocked ureter depending on the sex of the fetus. Administration of a single dose of DMO between gestational day 9 and 10.3 produced both renal agenesis and ureters of varying lengths. Some ureters were of normal length with a tuft of one or two nephrons at their tip, while others were one half or one quarter of their normal length. In some instances the ureter was completely absent. The reason for this strong effect on the ureter is unknown.     

The phylogenetic distribution of the ampulla ureter and ampulla urogenital/uriniferous papilla in the Serpentes

The ampulla ureter and ampulla urogenital/uriniferous papilla represent differing morphologies of the caudal urogenital ducts in snakes. The ampulla ureter is an enlarged portion of the caudal extremity of the ureter that communicates the cranial regions of the ureter and the ductus deferens/Wolffian duct to the urodaeum. The ampulla urogenital/uriniferous papilla is an enlarged pouch, distinct from the ureter, which communicates the ureter and ductus deferens/Wolffian duct to the urodaeum. Although functional differences of these two structures are unknown, the ampulla urogenital/uriniferous papilla may have evolved for urine storage in males and females, and secondarily evolved a reproductive function in males. The most parsimonious optimization of the ampulla ureter and ampulla urogenital/uriniferous papilla indicates that the ampulla ureter is the ancestral state in snakes. Examining the presence or absence of the ampulla ureter and ampulla urogenital/uriniferous papilla in snakes on conflicting caenophidian phylogenies results in two hypotheses for the evolution of these variant morphologies: (1) The ampulla urogenital/uriniferous papilla evolved from the ampulla ureter independently in the Colubroidea and Elapoidea with subsequent losses of the ampulla urogenital/uriniferous papilla in the Elapoidea and (2) a single transition from the ampulla ureter to the ampulla urogenital/uriniferous papilla on the branch leading to the Colubroidea + Elapoidea with subsequent losses of the ampulla urogenital/uriniferous papilla in the Elapoidea and Colubroidea. The presence of the ampullae urogenital/uriniferous papilla in only the Colubroidea and Elapoidea highlights the affinity of these two taxonomic groups, a relationship that is strongly supported in published cladograms produced with molecular datasets.     

A two way fully coupled fluid structure simulation of human ureter peristalsis

Abstract

Numerical simulations of ureter peristalsis have been carried out in the past to understand both the flow field and ureter wall mechanics. The main objective of the current investigations is to have a better understanding of the urine transport due to the peristalsis in the ureter, thus making the information helpful for a better treatment and diagnosis of ureteral complications like urine reflux. In the current study, a numerical simulation is performed using a finite-element-based solver with a two-way fully coupled fluid structure interaction approach between the ureter wall and urine. For the first time, the ureter wall is modeled as an anisotropic hyper-elastic material based on experiments performed in previous literature on the human ureter. Peristalsis in the ureter is modeled as a series of isolated boluses. By observing the flow field it is clear that the peristalsis mechanism has a natural tendency to create a backflow as the isolated bolus moves forward. As a result, the urine can flow back from the bladder to the ureter at the ureterovesical (ureter-bladder) junctions, if the one-way valve starts to malfunction.     

输尿管子宫内膜异位症伴肾积水1 例报告并文献复习

目的:探讨子宫内膜异位症累及输尿管的诊断和治疗方法。方法:术前诊断为右侧输尿管下段占位病变伴右肾积水的42岁女性患者,行下腹正中切口,探查右侧输尿管开口处可见淡黄色息肉样病变,突入膀胱,输尿管下段增粗并全程扩张积水,行输尿管下段并膀胱袖式切除,输尿管膀胱再植术。术后病理报告为输尿管子宫内膜异位症。结果:术后复查B超示右肾积水较术前恢复,术后予抑那通3.75mg/28d,随访6个月未见复发。结论:对于输尿管占位并上尿路积水的女性患者,除考虑肿瘤外还应考虑子宫内膜异位症可能。手术联合内分泌治疗是治疗输尿管子宫内膜异位伴肾积水的有效方法。     

Calcitonin gene-related peptide (CGRP)-immunoreactive nerve plexuses in the renal pelvis and ureter of rats

Summary The distribution of calcitonin gene-related peptide-immunoreactive nerve fibers in the renal pelvis and ureter was examined by immunohistochemistry using whole-mount preparations and cryostat sections. The patterns of innervation were contrasted between the pelvis and ureter; the immunoreactive nerve fibers in the pelvis ran parallel to the long axis of each of the circular and longitudinal muscle layers, causing a lattice-like appearance of the nerve fibers. In the ureter, the immunoreactive fibers were accumulated in the subepithelial region and the longitudinal muscle. In both the pelvis and ureter, a portion of the nerve fibers of smaller caliber showed a swollen or beaded structure; they were located in the musculature and beneath the epithelium extending for considerable distances. Ligation of the ureter caused a marked decrease in the immunoreactive nerves in the pelvis and the proximal portion of the ureter, suggesting that the axonal flow in the calcitonin gene-related peptide-containing neurons of the ureter runs towards the pelvis.     

The removal of stones from low in the ureter; a report on an improved method

Extraction of stones from the lower part of the ureter can be facilitated by use of a long filiform which permits the attachment and introduction of dilating Phillips catheters of increasing caliber and of various stone extractors. The filiform must be left in place, with the tip superior to the stone, until the ureter has been successfully dilated, the stone extracted and a drainage catheter inserted. The filiform serves to guide the instruments up the ureter. Smooth muscle relaxation, or "tone paralysis," is achieved by leaving each dilating catheter in the ureter for at least ten minutes.A combination of spinal and local anesthesia is used, and this contributes further to the desired ureteral relaxation. This simple method was used successfully in 34 of 35 consecutive cases to remove a stone in the lower part of the ureter.