I.V.).
Preparation of the bladder and recording of the flow volume
The upper half of the urethra about 2-3 cm distal to the bladder neck was incised and a catheter (Fr 5) was inserted. The catheter was connected via a three-way stopcock to a syringe, or to a low pressure transducer (LPU-0·1, Nihon Kohden, Japan) for measurement of the intravesical pressure.
The apex of the bladder was incised and a plastic tube with an inner diameter (i.d.) of 9 mm was inserted for isotonic distension of the bladder. As illustrated in Fig. 1A, the plastic tube, a probe (i.d., 6 mm) of the electromagnetic blood flow meter and a reservoir were connected by a thick rubber tube (i.d., 10 mm). The surface area of the reservoir is large enough (about 300 cm2), so that the fall-off of applied pressure is only 3·3 mmH2O in an extreme case when 100 ml of fluid should flow from the reservoir to the bladder. The reservoir and the connecting tubes were filled with 0·9 % saline at room temperature (24-26°C). Constant pressures between 30 and 1000 mmH2O were applied to the bladder by opening the stopcock to the reservoir for 8 min. One minute after closing the stopcock, fluid in the bladder was withdrawn with a syringe and the volume was measured. After waiting for 5-10 min and verifying that the bladder was empty, the next constant pressure was applied. The flow rate (ml min-1) of saline through the probe, between the bladder and the reservoir, was measured with an electromagnetic blood flow meter (MFV-3100, Nihon Kohden; DC-30 Hz (-3 dB)), and the volume within the bladder was obtained by integrating the flow rate with an integrator (EI-601G, Nihon Kohden).
Isovolumic recording was made in all preparations. A large micturition contraction-relaxation rhythm could be evoked by turning off the stopcock or clamping the rubber tube near the bladder, and by filling the bladder with the appropriate amount of fluid.
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Figure 1. Experimental set-up for isotonic recording
A reservoir, the probe of an electromagnetic flow meter and the bladder were connected with thick tubes and were filled with saline. The bladder was isotonically distended by opening a stopcock. The urethra was cannulated for measurement of the intravesical pressure or for injecting or withdrawing the intravesical fluid. The volume flowing through the probe was measured by integrating the output (ml min-1) from the electromagnetic flow meter.
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Dissection, recording and stimulation of the peripheral nerves
Bladder motility was examined in preparations with bladder nerves intact, or after lesion of the hypogastric and/or pelvic nerves. Hypogastric nerves were dissected bilaterally just distal to the hypogastric ganglion. All the pelvic nerve branches coursing towards the bladder were dissected bilaterally between the bladder and the major pelvic plexus.
For recording the efferent nerve activity, one of the bladder branches of the pelvic nerve was dissected free as close as possible to the bladder. The efferent activity was recorded by bipolar Ag-AgCl hook electrodes from a central end of the severed nerve within a pool of paraffin oil. The bladder base was held in place with a small spatula for stable recordings of the efferent activity. The activity was amplified with a preamplifier (AB-651J, Nihon Kohden) (low cut; 50 Hz). In two animals, the same bladder nerve branch was electrically stimulated with a 200 µs pulse.
The volume flowing to the bladder, the intravesical pressure, and the efferent nerve activity were monitored by an oscilloscope, and recorded on a thermal array recorder (RTA-1200M, Nihon Kohden) and on a tape with a PCM data recorder (PC-108M, Sony Magnescale, Japan; DC-48 kHz). Efferent nerve activities were replayed and spikes were counted with a pulse-counting unit (QC-111J and ET-612J, Nihon Kohden) after cessation of the experiments.
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RESULTS |
Bladder motility during isotonic recording
Preparation with bladder nerves intact. Figure 2A-F shows typical bladder responses when the empty bladder was isotonically distended. After an initial rapid flow of saline into the bladder from the reservoir, the bladder kept a fairly constant volume at low pressures (Fig. 2A and B). The intravesical volume showed small inflow-outflow fluctuations at frequencies of ca 10 times min-1. Concomitant with these fluctuations, a small rise of less than 10 mmH2O in the intravesical pressure was observed. At higher pressures, the bladder started to partially expel its volume to the reservoir within half a minute (from triangle in Fig. 2C-F), and maintained a nearly constant volume (Fig. 2C) or expanded gradually (Fig. 2D and E) with inflow-outflow fluctuations at somewhat higher frequencies (12-20 times min-1). Abrupt expansion of the bladder was often observed, as indicated by an arrow in Fig. 2E and F. Figure 2H shows the relation between the clamped pressure and the intravesical volume when the bladder expelled fluid maximally (open circles) or the final volume at cessation of the isotonic distension (filled circles). Expulsion of fluid was observed at more than 150 mmH2O. The final volume at cessation of the distension fell as the clamped pressure was raised to 350 mmH2O, and then gradually increased up to 700 mmH2O. Above that pressure, the intravesical volume increased dramatically, showing a steep slope in the pressure-volume relation curve (from arrow). The final volume calculated from the flow meter was almost identical to the final volume, measured roughly by withdrawing the fluid from the bladder after cessation of each test (crosses), indicating the validity of the measurement in the present study. Similar profiles to those shown in Fig. 2H were observed in all animals (n = 5). In three animals where the pressure clamp was applied for a longer duration (10-15 min), the bladder tended to continue expanding slightly even after 8 min. The pressure-volume relation, however, was quite similar to that obtained when the intravesical pressure was clamped for 8 min.
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Figure 2. Bladder response evoked during isotonic recording
A-F, representative data showing the volume flowing to the bladder from the reservoir (upper traces) in response to the isotonic distension of the empty bladder for 8 min (lower traces). Dotted lines indicate that bladder volume is 0 ml. Triangles (C-F) indicate the onset of when the bladder started to partially expel its volume to the reservoir. Arrows (E and F) indicate the onset of abrupt expansion of the bladder. Between arrowheads (E), the bladder expanded with intermittent inflows of fluid. H, plot of intravesical volume against clamped pressure when the bladder expelled its fluid maximally ( ) or the final volume at cessation of the isotonic distension ( ) as illustrated in G. Arrow indicates the point from which the slope of this relation becomes steep. , volume measured roughly by withdrawing the fluid from the bladder 1 min after cessation of the isotonic distension. Filled circle indicated by arrowhead represents data where the bladder was distended for 5 min.
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After lesion of the hypogastric nerves. The bladder response after lesion of the hypogastric nerves (n = 8) was essentially similar to that before lesion of the nerves, showing small inflow-outflow fluctuations, expelling fluid in the initial phase (from triangle in Fig. 3A), keeping a constant volume at lower pressures, expanding gradually or abruptly (arrows in A) at higher pressures, and showing a steep slope in the pressure-volume relation in the higher pressure range (filled circles in D; from arrow). One difference was that the volume flowing to the bladder at low pressures tended to be smaller than that in the intact preparations (cf. filled circles in Figs 2H and 3D at intravesical pressures of less than 200 mmH2O), probably reflecting the absence of an active relaxation mechanism caused by the hypogastric nerves.
After combined lesion of the hypogastric and pelvic nerves. As exemplified in Fig. 3B, additional bilateral lesion of the pelvic nerves (see Fig. 3C) dramatically diminished the inflow-outflow fluctuations in both frequency (6-8 times min-1) and amplitude, and the bladder expanded almost exponentially at any level of the clamped pressure (n = 11). When comparing the pressure-volume relations of this preparation (triangles in Fig. 3D) with that before lesion of the pelvic nerves (filled circles), the final volume in the former was much larger than that in the latter preparation.
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Figure 3. Bladder response evoked during isotonic recording before and after lesion of the pelvic nerves
A and B show representative data before and after bilateral lesion of the pelvic nerves. Explanations including symbols (triangle, arrow) are the same as in Fig. 2A-F. The hypogastric nerves had already been lesioned as illustrated in C. Crosses in C indicate the transsection of the pelvic nerves. D, plot of intravesical volume at cessation of the isotonic distension (see inset) against clamped pressure. , lesion of the hypogastric nerves;  , after additional lesion of the pelvic nerves. Arrow indicates the point from which the slope of this relation becomes steep.
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After lesion of the pelvic nerves. In one animal, the pelvic nerves were lesioned bilaterally leaving the hypogastric nerves intact. As expected, this procedure dramatically diminished the inflow-outflow fluctuations in both frequency and amplitude when the bladder was isotonically distended, and the bladder expanded almost exponentially, in a similar way to the bladder response in preparations after combined lesion of the hypogastric and pelvic nerves. The final volume in the pressure-flow relation was almost identical to that after additional lesion of the hypogastric nerves.
Efferent activity of the pelvic nerve
Lesion studies showed that the efferent activity of the pelvic nerve appeared to be still active even at high pressure levels, regardless of the enormous expansion of the bladder. To clarify the above assumption and to deduce a possible inhibitory mechanism explaining the relaxation following micturition contraction, efferent activities of the bladder branch of the pelvic nerve were examined. The hypogastric nerves had already been lesioned to avoid possible interaction in the recording of the efferent activity (see Fig. 5B).
Figure 4A-C shows the efferent activity of the pelvic nerve together with the intravesical volume and the pressure. For each applied pressure, the efferent activity started to increase within 10 s and reached an almost steady firing level, which was interposed with transient decreasing phases of duration less than 26 s at irregular intervals. The volume flowing to the bladder was larger at higher pressures, as already observed. The efferent activity at the steady firing phase increased when raising the applied pressure (also see filled circles in D). The efferent activity in another example also showed a pressure-dependent increase (open circles in D), and reached a maximum at almost 590 mmH2O (indicated by arrow). An increase in activity was already observed at 70 mmH2O in this case. Such a pressure-firing relation was observed in another five animals.
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Figure 4. Efferent activity of the pelvic nerve evoked during isotonic recording
A-C, representative data showing efferent activity of the bladder branch of the pelvic nerve and its firing rate together with intravesical volume and intravesical pressure. The hypogastric nerves had been lesioned bilaterally (see Fig. 5B). The decrease in efferent activity occurs when the bladder expands transiently (B) or gradually (C) as indicated by dashed arrows which correspond to the onset or end of the expansion. D, plot of firing rate against clamped pressure (). The mean firing rate at constant firing phase excluding the transient decreasing phase was plotted. Data taken from another animal are also plotted (). Arrow above the open circle indicates the point from which the slope of this relation shows a plateau.
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As shown in Fig. 5, the plateau level of efferent activity was clearly demonstrated when isotonic distension was applied stepwise every 2 min (n = 3). The efferent activity increased depending on the clamped pressure over the range 190-700 mmH2O, showing a plateau at higher pressures (Fig. 5A and filled circles in C). The intravesical pressure when the efferent activity reached a plateau (Pplateau) was estimated by interpolating straight lines on the rising phase and the plateau level (Fig. 5C): the crossing point gives a value of Pplateau (650 mmH2O in this case). The Pplateau was estimated to be 300-920 mmH2O in three animals. The value of the Pplateau was also estimated in the same manner in cases when the bladder was distended for 8 min. The Pplateau shown in Fig. 4D was estimated to be 590 mmH2O (open circle indicated by arrow), and 770 mmH2O assuming that the firing rate at 950 mmH2O is at a plateau level (filled circle). The value ranged from 500 to 800 mmH2O in seven animals. Note that the increase in intravesical volume was accelerated when the efferent activity was at the plateau (open circle in Fig. 5C), resulting in a bend in the pressure-volume relation (from arrow).
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Figure 5. Efferent activity of the pelvic nerve when raising the intravesical pressure stepwise
A, efferent activity of the bladder branch of the pelvic nerve, its firing rate, intravesical volume and intravesical pressure. The hypogastric nerves had been lesioned bilaterally and recordings were made from one branch of the pelvic nerve as illustrated in B. Large deflections in the efferent activity (indicated by dots) are artifacts occurring while raising the pressure, which are also counted in the firing rate. C, plot of firing rate of the efferent activity () or volume at the end of each pressure () against clamped pressure. The crossing point of the dashed lines interpolated from the rising phase and the plateau level of the filled circles gives the estimated value of the intravesical pressure when the efferent activity reaches a plateau (Pplateau). Arrow above the open circle indicates the point from which the slope of the pressure-volume relation becomes steep (Pbend).
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Having a plateau at higher pressures indicated that there is an upper limit in the central output in the micturition reflex pathway. The relation between the Pplateau and the peak pressure of micturition contraction-relaxation rhythm during isovolumic recording was then examined. Peak pressure value was obtained by averaging the peak pressure of three to five micturition contractions evoked during isovolumic recording in the same animal, and the value ranged between 420 and 860 mmH2O. When relating the Pplateau with the peak pressure of micturition contraction (Fig. 6A), two parameters were positively correlated in the group where the bladder was distended for 8 min (filled circle; r = 0·9, P < 0·02, n = 7), and the plots including open circles, which were obtained by distending the bladder stepwise, were distributed around the straight line with a slope of unity. As expected from the relation, the mean value of Pplateau (649 mmH2O; pooled data of both groups) almost equalled the mean value of the peak pressure of micturition contraction (661 mmH2O).
It appears from Fig. 5C that the pressure causing the bend in the pressure-volume relation (Pbend) was related to the Pplateau, and thus the peak pressure of micturition contraction. The Pbend was examined in preparations with bladder nerves intact and after lesion of the hypogastric nerves (see arrow in Figs 2H and 3D, respectively). The value of the Pbend ranged from 170 to 550 mmH2O in intact (n = 8) and from 250 to 810 mmH2O in preparations after lesion of the hypogastric nerves (n = 8). When relating these values with the peak pressure of the micturition contraction (Fig. 6B), the two parameters were positively correlated in both intact (open circle; r = 0·9, P < 0·005) and lesioned preparations (filled circle; r = 0·9, P < 0·0005). The plots were distributed below the straight line with a slope of unity in both groups. The mean value of Pbend (444 mmH2O; pooled data of both groups) was smaller than the mean value of the peak pressure of micturition contraction (672 mmH2O).
Transient expansion
It was also noted in Fig. 4A-C that the efferent activity showed transient decreases whatever the applied pressure. Concurrent with these periods, the bladder transiently expanded; the initiation and the end of the expansion were fairly coincident with the initiation of the decrease and increase of the efferent activity, respectively (e.g. between dashed lines in Fig. 4B), implying that the transient expansion was a result of the decrease in the efferent activity. In contrast to the recovery of the efferent activity to the steady firing level, the intravesical volume did not always return to the previous level. A small but prolonged decrease of the efferent activity also appeared to be related to a gradual expansion of the bladder (between dashed lines in Fig. 4C).
The duration of the transient expansion was examined in all traces in preparations with bladder nerves intact (8 animals) or after lesion of the hypogastric nerves (10 animals). Since the bladder showed inflow-outflow oscillations with relatively constant frequency and amplitude, an amplitude more than twice that of the oscillations was regarded as a transient expansion caused by the decrease in efferent activity (downward arrows in Fig. 7A). Traces were excluded from the analysis if expansions did not satisfy the above criteria. Only the duration with the largest amplitude in each trace was measured from the onset to the end of the expansion as indicated by the dashed lines in Fig. 7A. The duration of the transient expansion ranged from 3 to 33 s (mean ± S.D.: 12·3 ± 7·6 s, n = 41) in intact, and from 3 to 27 s (10·2 ± 5·4 s, n = 44) in preparations after lesion of the hypogastric nerves; no difference was observed between the two groups (P > 0·15; Student's two tailed t test). When relating the duration of the transient expansion with the clamped pressure (Fig. 7B), no correlation was observed for either preparation (r = 0·2, P > 0·2 in intact (open circle); r = 0·01, P > 0·9 in lesioned (filled circle and cross)). Figure 7B also shows that the transient expansion occurred over a wide range of applied pressure (100-1030 mmH2O), even when analysing only one animal (crosses in B). The smallest pressure causing a transient expansion was 220 mmH2O in this case, with the range being distributed between 100 and 470 mmH2O (Fig. 7C).
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Figure 7. Duration of transient expansion and the relation with applied pressure
A, example trace showing transient expansions interposed between inflow-outflow oscillations with relatively constant frequency and amplitude. Inflows with amplitudes of more than twice that of the inflow-outflow oscillations were regarded as transient expansions caused by the decrease in efferent activity (downward arrows). The duration was measured from the onset to the end of the expansion as indicated by dashed lines. B, plot of duration of the transient expansion against applied pressure in preparations with bladder nerves intact () or after lesion of the hypogastric nerves (). , data taken from an animal whose hypogastric nerves had been lesioned, for example. C, histogram showing the smallest pressure causing transient expansion in each preparation.
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Figure 8 (A-C) shows the effect of intravesical volume on the micturition contraction-relaxation rhythm. The volume was increased stepwise by infusing 0·5-2 ml of saline. The steep slope of the base pressure at large volumes (filled circle in B) may be caused mainly by passive extension of the bladder. In this condition, the mean values of the rhythm interval (open circle in C; see inset) and the relaxation period (filled circle) were shortened up to 32 and 24 s, respectively, as the intravesical volume was increased. The shortest relaxation period was 16 and 20 s in two other animals. Shortening of the mean relaxation period to 12-23 s was also observed in two animals when the central cut end of the bladder branch of the pelvic nerve was repetitively stimulated (1-30 V, 5-200 Hz; see Fig. 8D). The shortened values for the relaxation period in these two experiments were within the range of the duration of the transient expansion evoked during isotonic recording of the bladder (Fig. 7B).
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DISCUSSION |
The present study analyses bladder motility and the efferent activity under isotonic and isovolumic conditions to elucidate the central mechanism producing the micturition contraction-relaxation rhythm.
Inflow-outflow fluctuations
The bladder showed inflow-outflow fluctuations in volume of relatively high frequency consistent with previous studies (Mellanby & Platt, 1939, 1940). Inflow-outflow fluctuations of small amplitude still remained after lesion of the pelvic nerves, indicating that they were produced, at least partly, at peripheral sites. Since ganglia are present in the bladder wall, the local circuit between the bladder and the postganglionic neurones may be involved (Jänig & McLachlan, 1987). Although the efferent activity showed a rhythmic firing correspondent to the inflow-outflow fluctuations when the frequency of the fluctuation was low, the relation between them became unclear as the frequency of the fluctuations increased, usually at high constant pressures (M. Sasaki, unpublished observation). It therefore appears that the central nervous system (CNS) may amplify the inflow-outflow fluctuation but that the CNS itself does not produce a rhythm for the fluctuation.
Excitability of the CNS regulating the bladder activity
The present study shows that the contraction and the transient expansion of the bladder were caused by changes in pelvic nerve activity as a peripheral limb of the reflex pathway. Considering that sacral or pelvic afferents from the bladder show a static firing when the bladder is isotonically distended (Häbler et al. 1993), the central mechanism regulating the bladder activity can be treated simply as an apparatus that converts tonic pelvic afferent inputs to various patterns of output in the present experimental protocol. Possible converting sites may involve various regions including pons, sacral area, and other related areas such as the periaquedactal grey where information from pelvic afferents is sent (see de Groat, 1993; Blok, de Weerd & Holstege, 1995). The activity of the efferent pelvic nerves to the bladder consists of three phases: an initial increasing phase, a relatively static firing phase and a transient decreasing phase.
The efferent activity gradually increased in the initial phase of isotonic distension, implying that the micturition reflex pathway is activated gradually rather than by an all-or-none switching mechanism. Considering that the afferent activity shows an abrupt increase (Häbler et al. 1993), the gradual increase in the efferent activity indicates that in the micturition reflex pathway, the CNS can resist a sudden increase of the bladder pressure for a short while. This is consistent with observations that a micturition contraction is not evoked immediately after increasing the intravesical pressure above the micturition threshold by infusing a fluid to the quiescent bladder, or that electrical stimulation of the pelvic nerve afferents produces no evoked responses in the pelvic efferents when the bladder is quiescent (de Groat et al. 1982; McMahon & Morrison, 1982). Possible mechanisms explaining the initial gradual increase might be a polysynaptic pathway activating process, a predominant activation of a central inhibitory mechanism against a sudden increase of the intravesical pressure, or a disinhibitory process of tonic inhibition of the micturition pathway. Existence of a tonic GABAergic and enkephalinergic inhibition on the pontine micturition centre has been suggested (Mallory, Roppolo & de Groat, 1991).
The efferent activity in the static firing phase increased as the pressure level was raised, reaching a plateau at the higher pressure range (see Figs 4 and 5). Similar profiles have been reported in the sacral parasympathetic neurones to the bladder, and they reach a maximum at pressures below 300 mmH2O, concluding that the preganglionic neurone receives a maximal synaptic input when intravesical pressure exceeds the micturition threshold (de Groat et al. 1982; also see de Groat & Ryall, 1969). In the present study, however, Pplateau (300-920 mmH2O) was higher than in their reports, and far beyond micturition threshold. In their figure (Fig. 2E of de Groat & Ryall, 1969), the firing rate of a preganglionic neurone appears to increase when raising the intravesical pressure up to 500 mmH2O, implying that Pplateau is higher in this neurone, which is consistent with the present study.
The activity of some sacral afferent fibres from the bladder has been shown to increase with increasing intravesical pressures of up to at least 100 mmHg (= 1360 mmH2O) (Häbler, Jänig & Koltzenburg, 1990, 1993), indicating that the afferent activity continues to increase at higher pressure ranges where the efferent activity shows a plateau. This suggests that the CNS basically operates as an amplifier of the afferent inputs, but that there is an upper limit to the CNS output even when stronger afferent inputs occur. The present study shows that the peak pressure of a micturition contraction almost equalled Pplateau, further suggesting that the peak pressure is determined by the saturating level of the central output. The large increase in final volume in the higher pressure range (Figs 2, 3 and 5) could thus be explained, at least partly, by an overload of applied pressure once the efferent activity has already saturated.
Although the threshold pressure causing the firing increase of the efferent activity was not examined minutely, the efferent activity had already increased at values below the micturition threshold pressure in most cases. As exemplified in Fig. 4D (open circle), the firing increase was observed at 70 mmH2O, where the bladder showed a contraction- relaxation rhythm with small amplitude (10-40 mmH2O) and relatively high frequency (3-4 times min-1) under isovolumic conditions. The micturition threshold was 100 mmH2O in this case. It seems likely that the micturition reflex pathway can be activated below the micturition threshold, but that afferent input is insufficient to drive the self-reinforcing feedback.
Neural mechanism triggering relaxation
The bladder showed gradual or transient expansions under isotonic conditions. Transient expansion was closely related to the decrease of the activity of efferent pelvic nerves. Gradual expansion, which was often composed of several inflows of short duration (between arrowheads in Fig. 2E), also appeared to be caused by a small and rhythmic decrease in the efferent activity (between arrows in Fig. 4C). Since such expansions were not observed in preparations after lesion of the pelvic nerves even when the hypogastric nerves were intact, afferent and efferent pathways related to these expansions are exclusively via pelvic nerves. Considering that the activity of the sacral bladder afferents is static under isotonic conditions (Bahns, Halsband & Jänig, 1987; Häbler et al. 1993), it is concluded that this reduction is caused centrally, possibly by some inhibitory neural mechanism. It was also noted that the efferent activity of the pelvic nerve was not completely suppressed in this phase, indicating that the inhibitory mechanism does not switch off the micturition reflex pathway completely.
The durations of the transient expansions were short (3-33 s) compared with the relaxing period observed during micturition contraction-relaxation rhythm (1-3 min). The present study, however, demonstrates that the relaxing period could be shortened to 12-24 s by increasing the intravesical volume or by repetitive stimulation of the central end of the pelvic nerve. The results suggest that central inhibitory mechanisms can act for short periods even under isovolumic conditions. A brief inhibition of the efferent activity may be enough for cessation of the micturition contraction considering that the pressure falls almost to a baseline level within 20 s; the decrease of both afferent and efferent activities during this falling phase (de Groat & Ryall, 1969) will inhibit further a subsequent increase in pressure. When the inhibition is too short, however, the pressure may increase again - a phenomenon often observed during micturition contractions (see, for example, Fig. 8D, indicated by arrows).
The long-lasting relaxation may be attributed partly to the low activity of the pelvic afferents at around baseline pressure. In addition, a weak inhibition might remain for a while, since the bladder contraction evoked by electrical stimulation of the pontine micturition centre is depressed immediately after the end of micturition contraction and progressively recovers in amplitude with time (Kruse, Mallory, Noto, Roppolo & de Groat, 1992).
Transient expansion occurring over a wide range of applied pressure implies that the inhibitory mechanism can be activated at any pressure, and not because the intravesical pressure reaches a maximum. The fairly constant pressure of the micturition contraction may be explained by a rapid increase of the pressure before the inhibitory mechanism is activated. A functional implication of the inhibitory mechanism might be that it could cause a reflex relaxation of the bladder to prevent micturition in an emergency.
The threshold pressure causing transient expansion was low (100-470 mmH2O). This pressure range excites mainly the myelinated afferent fibres from the tension receptor in the bladder (Häbler et al. 1993), whereas the unmyelinated fibres start to fire at above 400 mmH2O (Häbler et al. 1990). Thus the result suggests that at least myelinated afferent fibres can trigger the central inhibitory mechanism as well as excitatory mechanism.
Kruse, Noto, Roppolo & de Groat (1990) have postulated a local 'off-switch' circuit that inhibits micturition contraction within the laterodorsal tegmental nucleus, the periaqueductal grey or the lateral parabrachial nucleus of rats, since electrical stimulation of these areas induces a short-lasting inhibition of an on-going bladder contraction. The existence of inhibitory inputs to the pontine micturition centre has been revealed by a chemical stimulation study in cats (Mallory et al. 1991; de Groat, 1993). The present study suggests the existence of inhibitory neurones that increase their firing rate transiently concomitant with bladder relaxation. If such neuronal activity can be recorded in some area of the CNS, it could indicate the inhibitory area causing bladder relaxation.
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Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (06680816).
Correspondence
M. Sasaki: Department of Physiology, Tokyo Medical College, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160, Japan.
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M. Sasaki
Feed-forward and feedback regulation of bladder contractility by Barrington's nucleus in cats
J. Physiol.,
May 15, 2004;
557(1):
287 - 305.
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Introduction
-chloralose (initial dose, 40-50 mg kg-1 
