Activation and inhibition of the micturition reflex by penile afferents in the cat

Coordination of the urinary bladder and the external urethral sphincter is controlled by descending projections from the pons and is also subject to modulation by segmental afferents. We quantified the effects on the micturition reflex of sensory inputs from genital afferents traveling in the penile component of the somatic pudendal nerve by electrical stimulation of the dorsal nerve of the penis (DNP) in alpha-chloralose anesthetized male cats. Depending on the frequency of stimulation (range, 1-40 Hz), activation of penile afferents either inhibited contractions of the bladder and promoted urine storage or activated the bladder and produced micturition. Stimulation of the DNP at 5-10 Hz inhibited distension-evoked contractions and increased the maximum bladder capacity before incontinence. Conversely, stimulation at 33 and 40 Hz augmented distension-evoked contractions. When the bladder was filled above a threshold volume (70% of the volume necessary for distension-evoked contractions), stimulation at 20-40 Hz activated de novo the micturition reflex and elicited detrusor contractions that increased voiding efficiency compared with distension-evoked voiding. Electrical stimulation of the DNP with a cuff electrode or percutaneous wire electrode produced similar results. The ability to evoke detrusor contractions by activation of the DNP was preserved following acute spinal cord transection. These results demonstrate a clear role of genital afferents in modulating the micturition reflex and suggest the DNP as a potential target for functional restoration of bladder control using electrical stimulation.     

Mechanical responses of the rat uterus, cervix, and bladder to stimulation of hypogastric and pelvic nerves in vivo

Mechanical activities of the uterus, cervix, and bladder were recorded in vivo in anesthetized rats during electrical stimulation of either the hypogastric or pelvic nerve. Ovariectomized controls and hormone-treated groups were used as well as pregnant and postpartum rats. Stimulation of either hypogastric or pelvic nerve produced voltage- and frequency-dependent contractions of the three organs with no evidence of apparent inhibition. All evoked responses were completely abolished by tetrodotoxin, suggesting that these nerves are common pathways of innervation to the three organs. Atropine abolished uterine and cervical responses to both hypogastric and pelvic nerve stimulation, whereas bladder responses were only partly reduced. Hexamethonium almost totally blocked the evoked responses of the uterus and cervix. Phentolamine partly blocked uterine and cervical responses, and propranolol or physostigmine enhanced uterine and cervical responses to both hypogastric and pelvic nerve stimulation. These results suggest that motor innervation to the rat uterus and cervix is predominantly postganglionic cholinergic, with some alpha- and beta-adrenergic components, and that the bladder is innervated by mainly cholinergic and also noncholinergic nerves. Estrogen and estrogen-plus-progesterone pretreatment significantly increased the responses of uterus and cervix but not bladder. Uterine and cervical responses to either hypogastric or pelvic nerve stimulation were markedly reduced late in pregnancy and reappeared within 7 days after delivery.     

Role of pudendal afferents in voiding efficiency in the rat

The reciprocal activities of the bladder and external urethral sphincter (EUS) are coordinated by descending projections from the pontine micturition center but are subjected to modulation by peripheral afferent inputs. Transection of the somatic pudendal nerve innervating the striated EUS decreases voiding efficiency and increases residual urine in the rat. The reduction in voiding efficiency was attributed to the lack of phasic bursting activity of the EUS following denervation. However, transection of the pudendal nerve also eliminates somatic sensory feedback that may play a role in voiding. We hypothesized that feedback from pudendal afferents is required for efficient voiding and that the loss of pudendal sensory activity contributes to the observed reduction in voiding efficiency following pudendal nerve transection. Quantitative cystometry in urethane anesthetized female rats following selective transection of pudendal nerve branches, following chemical modulation of urethral afferent activity, and following neuromuscular blockade revealed that pudendal nerve afferents contributed to efficient voiding. Sensory feedback augmented bladder contraction amplitude and duration, thereby increasing the driving force for urine expulsion. Second, sensory feedback was necessary to pattern appropriately the EUS activity into alternating bursts and quiescence during the bladder contraction. These findings demonstrate that the loss of pudendal sensory activity contributes to the reduction in voiding efficiency observed following pudendal nerve transection, and illustrate the importance of urethral sensory feedback in regulating bladder function.     

Effects of bradykinin mediated by autonomic efferent nerves

Intra-arterial injections of bradykinin cause increases in blood pressure and increased impulse rates in single sympathetic efferent fibres. The peptide also causes one or more large bladder contractions, which are associated with increased impulse rates in pelvic nerve efferent fibres whose spontaneous discharges are temporally associated with increases in intravesical pressure. These induced increases in pelvic nerve discharge and intravesical pressure could be abolished or greatly reduced by interference with conduction in pathways which mediate reflex bladder contractions. It is concluded that bradykinin has little direct action on the bladder, and that the large contractions which result from its administration are mediated by the central nervous system.     

Neuromodulation in a rat model of the bladder micturition reflex

A rat model of bladder reflex contraction (BRC) was used to determine the optimal frequency and intensity of spinal nerve (SN) stimulation to produce neuromodulation of bladder activity and to assess the therapeutic mechanisms of this neuromodulation. In anesthetized female rats (urethane 1.2 g/kg ip), a wire electrode was used to produce bilateral stimulation of the L6 SN. A cannula was placed into the bladder via the urethra, and the urethra was ligated to ensure an isovolumetric bladder. Saline infusion induced BRC. Electrical stimulation of the SN produced a frequency- and intensity-dependent attenuation of the frequency of bladder contractions. Ten-herz stimulation produced maximal inhibition; lower and higher stimulation frequency produced less attenuation of BRC. Attenuation of bladder contraction frequency was directly proportional to the current intensity. At 10 Hz, stimulation using motor threshold pulses (T(mot)) produced a delayed inhibition of the frequency of bladder contractions to 34 ± 11% of control. Maximal bladder inhibition appeared at 10 min poststimulation. High current intensity at 0.6 mA (～6 * T(mot)) abolished bladder contraction during stimulation, and the inhibition was sustained for 10 min poststimulation (prolonged inhibition). Furthermore, in rats pretreated with capsaicin (125 mg/kg sc), stimulation produced a stronger inhibition of BRC. The inhibitory effects on bladder contraction may be mediated by both afferent and efferent mechanisms. Lower intensities of stimulation may activate large, fast-conducting fibers and actions through the afferent limb of the micturition reflex arc in SN neuromodulation. Higher intensities may additionally act through the efferent limb.     

Commande nerveuse peripherique de l’erection

Local mechanisms causing penile erection and detumescence result from variation in tone of vascular and trabecular smooth muscles and in a lesser part of striated muscles around the crura penis. All these events are neurally mediated. We reviewed human and animal data concerning the functional peripheral neuroanatorny of erection. General organization of peripheral nervous system is recalled. Somatic efferents of the pudendal nerve, originating in the sacral spinal cord, innervate the striated musculature of the perineum. Somatic afferents of the penis are conveyed by the dorsal penile nerve, a branch of the pudendal nerve. Afferent terminations project into the spinal cord, their role is discussed. Parasympathetic pathways are involved in the reflexogenic erections. Sympathetic pathways destinated to the erectile structures are more complex. They are issued from thoracolumbar spinal cord and travel through the hypogastric nerve or the lumbosacral sympathetic chain. Sympathetic fibers originating in the sacral sympathetic chain are present in both pelvic and pudendal nerves. Inhibitory role on the erection of the sympathetic nervous system is well-known, it could be also responsible for psychogenic erections. Parasympathetic and sympathetic fibees are mixed in the pelvic plexus and the cavernous nerves which are described. Relations between the four sets of peripheral nerves (somatic efferents, penile afferents, thoracolumbar sympathetic sacral parasympathetic and sympathetic) are discussed.     

Analysis of the afferent limb of the vesicovascular reflex using neurotoxins, resiniferatoxin and capsaicin

The afferent limb of the vesicovascular reflex (VV-R) evoked by distension or contraction of the urinary bladder (UB) was studied in urethane-anesthetized female rats by examining the changes in VV-R after administration of C-fiber afferent neurotoxins [capsaicin and resiniferatoxin (RTX)]. Systemic arterial blood pressure increased parallel (5.1 to 53.7 mmHg) with graded increases in UB pressure (20 to 80 cm H(2)O) or during UB contractions. The arterial pressor response to UB distension was significantly reduced (60-85%) by acute or chronic (4 days earlier) intravesical administration of RTX (100-1,000 nM) or by capsaicin (125 mg/kg sc) pretreatment (4 days earlier). Chronic neurotoxin treatments also increased the volume threshold (>100%) for eliciting micturition in anesthetized rats but did not change voiding pressure. Acute RTX treatment (10-50 nM) did not alter the arterial pressor response during reflex UB contractions, whereas higher concentrations of RTX (100-1,000 nM) blocked reflex bladder contractions. It is concluded that VV-R is triggered primarily by distension- and contraction-sensitive C-fiber afferents located, respectively, near the luminal surface and deeper in the muscle layers of the bladder.     

Hindlimb muscular contraction reflexly decreases total pulmonary resistance in dogs

We have previously shown that contraction of the gracilis muscles of anesthetized dogs reflexly relaxes tracheal smooth muscle. We have also found that electrical stimulation of these afferents decreases total pulmonary resistance (TPR), a calculation that provides a functional index of airway caliber. Despite these findings, we have yet to show that muscular contraction reflexly decreases TPR. Therefore, in 11 alpha-chloralose-anesthetized dogs, we contracted the hindlimb muscles by electrically stimulating the L6-L7 ventral roots while measuring TPR breath by breath. We found that static contraction decreased TPR from 12.6 +/- 1.1 to 10.4 +/- 0.9 cmH2O X l-1 X s (P less than 0.05). This decrease was reflex in origin because it was prevented by section of the spinal roots innervating the working hindlimb. Repetitive twitch contractions (5 Hz) also reflexly decreased TPR, but the effect was smaller than that evoked by static contraction. The reflex decreases in TPR evoked by contraction were unaffected by propranolol but were abolished by atropine. We conclude that muscular contraction dilates the airways by a reflex mechanism whose efferent arm consists of a withdrawal of cholinergic input to airway smooth muscle.     

Urethral closure mechanisms under sneeze-induced stress condition in rats: a new animal model for evaluation of stress urinary incontinence

The urethral closure mechanism under a stress condition induced by sneezing was investigated in urethane-anesthetized female rats. During sneezing, while the responses measured by microtip transducer catheters in the proximal and middle parts of the urethra increased, the response in the proximal urethra was almost negligible when the bladder response was subtracted from the urethral response or when the abdomen was opened. In contrast, the response in the middle urethra during sneezing was still observed after subtracting the bladder response or after opening the abdomen. These responses in the middle urethra during sneezing were significantly reduced approximately 80% by bilateral transection of the pudendal nerves and the nerves to the iliococcygeous and pubococcygeous muscles but not by transection of the visceral branches of the pelvic nerves and hypogastric nerves. The sneeze leak point pressure was also measured to investigate the role of active urethral closure mechanisms in maintaining total urethral resistance against sneeze-induced urinary incontinence. In sham-operated rats, no urinary leakage was observed during sneeze, which produced an increase of intravesical pressure up to 37 +/- 2.2 cmH2O. However, in nerve-transected rats urinary leakage was observed when the intravesical pressure during sneezing exceeded 16.3 +/- 2.1 cmH2O. These results indicate that during sneezing, pressure increases elicited by reflex contractions of external urethral sphincter and pelvic floor muscles occur in the middle portion of the urethra. These reflexes in addition to passive transmission of increased abdominal pressure significantly contribute to urinary continence mechanisms under a sneeze-induced stress condition.     

CGRP immunoreactivity and NADPH-diaphorase in afferent nerves of the rat penis

Calcitonin gene-related peptide (CGRP)-immunoreactive afferent nerve fibers are abundant in the rat penis. In addition, NADPH-diaphorase, which stains for nitric oxide synthase, has been localized within both autonomic and sensory dorsal root ganglia (DRG) and may be part of an important biochemical pathway involved in penile tumescence. The purpose of this study was: 1) to examine the circuitry of afferent nerves that are CGRP immunoreactive from the L6 DRG, 2) to examine the possibility that there are NADPH-diaphorase-positive afferent fibers from the L6 DRG to the rat penis, and 3) to examine the localization and colocalization of CGRP and NADPH-diaphorase within L6 DRG afferent perikarya. Calcitonin gene-related peptide immunostaining in the penis was eliminated following a bilateral transection of the pudendal nerves, but was unchanged following a bilateral transection of the pelvic splanchnic or hypogastric nerves. The NADPH-diaphorase staining was not altered by any of the nerve transections. Injection of the retrograde axonal tracer fluorogold (FG) into the dorsum penis labeled perikarya in the L6 DRG. Although the majority of FG-labeled perikarya contained neither CGRP nor NADPH-diaphorase, small subpopulations of perikarya contained either CGRP immunoreactivity, NADPH-diaphorase, or both. A unilateral pudendal nerve transection virtually eliminated (>99%) FG labeling in the ipsilateral L6 DRG. These data suggest that NADPH-diaphorase and CGRP are present, either together or separately, within a subpopulation of penile afferent perikarya. In addition, CGRP-immunoreactive afferent nerve fibers reach the penis primarily via the pudendal nerves. Finally, NADPH-diaphorase-positive penile afferents may be another important source of nitric oxide (NO) for penile tumescence.     

Laryngeal motor control in frogs: Role of vagal and laryngeal feedback

Using decerebrate frogs (Rana catesbeiana), we investigated the role of vagal and laryngeal sensory feedback in controlling motor activation of the larynx. Vagal and laryngeal nerve afferents were activated by electrical stimulation of the intact vagal and laryngeal nerves. Pulmonary afferents were activated by lung inflation. Reflex responses were recorded by measuring efferent activity in the laryngeal branch of the vagus (Xℓ) and changes in glottal aperture. Two glottic closure reflexes were identified, one evoked by lung inflation or electrical stimulation of the main branch of the vagus (Xm), and the other by electrical stimulation of Xℓ. Lung inflation evoked a decrementing burst of Xℓ efferent activity and electrical stimulation of Xm resulted in a brief burst of Xℓ action potentials. Electrical stimulation of Xℓ evoked a triphasic mechanical response, an abrupt glottal constriction followed by glottal dilatation followed by a long-lasting glottal constriction. The first phase was inferred to be a direct (nonreflex) response to the stimulus, whereas the second and third represent reflex responses to the activation of laryngeal afferents. Intracellular recordings of membrane potential of vagal motoneurons of lung and nonlung types revealed EPSPs in both types of neurons evoked by stimulation of Xm or Xℓ, indicating activation of glottal dilator and constrictor motoneurons. In summary, we have identified two novel reflexes producing glottic closure, one stimulated by activation of pulmonary receptors and the other by laryngeal receptors. The former may be part of an inspiratory terminating reflex and the latter may represent an airway protective reflex. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 213–222, 1997     

Stimulation of groups III and IV phrenic afferents reflexly decreases total lung resistance in dogs

Little is known about the reflex effect on airway caliber evoked by stimulation of phrenic afferents. Therefore, in chloralose-anesthetized, paralyzed dogs, we recorded airflow, airway pressure, arterial pressure, and heart rate while electrically stimulating a phrenic nerve. Total lung resistance was calculated breath by breath. The phrenic nerve was stimulated at 3, 5, 20, 70, 140, and 200 times motor threshold and the compound action potential was recorded. Stimulation of the phrenic nerve at three and five times threshold, which activated groups I, II, and a few group III fibers, had no effect on any of the variables measured. Stimulation at 20 times threshold, which activated many group III fibers and groups I and II fibers, reflexly decreased resistance. Stimulation at 70, 140, and 200 times threshold, which activated groups I-IV fibers, evoked progressively greater decreases in lung resistance. The reflex bronchodilation evoked by phrenic nerve stimulation was unaffected by propranolol or phentolamine but was abolished by atropine. We conclude that activation of groups III and IV phrenic nerve afferents reflexly decreased total lung resistance by withdrawing cholinergic tone to airway smooth muscle.     

Convergence in Reflex Pathways from Multiple Cutaneous Nerves Innervating the Foot Depends upon the Number of Rhythmically Active Limbs during Locomotion

Neural output from the locomotor system for each arm and leg influences the spinal motoneuronal pools directly and indirectly through interneuronal (IN) reflex networks. While well documented in other species, less is known about the functions and features of convergence in common IN reflex system from cutaneous afferents innervating different foot regions during remote arm and leg movement in humans. The purpose of the present study was to use spatial facilitation to examine possible convergence in common reflex pathways during rhythmic locomotor limb movements. Cutaneous reflexes were evoked in ipsilateral tibialis anterior muscle by stimulating (in random order) the sural nerve (SUR), the distal tibial nerve (TIB), and combined simultaneous stimulation of both nerves (TIB&SUR). Reflexes were evoked while participants performed rhythmic stepping and arm swinging movement with both arms and the leg contralateral to stimulation (ARM&LEG), with just arm movement (ARM) and with just contralateral leg movement (LEG). Stimulation intensities were just below threshold for evoking early latency (<80 ms to peak) reflexes. For each stimulus condition, rectified EMG signals were averaged while participants held static contractions in the stationary (stimulated) leg. During ARM&LEG movement, amplitudes of cutaneous reflexes evoked by combined TIB&SUR stimulation were significantly larger than simple mathematical summation of the amplitudes evoked by SUR or TIB alone. Interestingly, this extra facilitation seen during combined nerve stimulation was significantly reduced when performing ARM or LEG compared to ARM&LEG. We conclude that locomotor rhythmic limb movement induces excitation of common IN reflex pathways from cutaneous afferents innervating different foot regions. Importantly, activity in this pathway is most facilitated during ARM&LEG movement. These results suggest that transmission in IN reflex pathways is weighted according to the number of limbs directly engaged in human locomotor activity and underscores the importance of arm swing to support neuronal excitability in leg muscles.     

Cerebral evoked potentials after rectal stimulation

We obtained reproducible cortical evoked potentials (EPs) in response to electrical stimulation of the rectum with 1 Hz frequency. We found 2 distinctly different EPs in response to rectal stimulation. In 5 females, the EP had an early onset latency (mean 26 msec) with multiple positive and negative peaks. In 10 females, the EP had a later onset latency (mean 52 msec) and a trifid configuration, having a very prominent negative peak. The early onset EPs after rectal stimulation appeared very similar to the wave form of the cortical EPs recorded after pudendal nerve stimulation. Finding similar interpeak latencies in the early onset EP after rectal stimulation and the EP after pudendal nerve stimulation suggests that either the same pathway was used or that rectal stimulation also stimulated the pudendal nerve. It appears that we stimulated visceral afferents when we recorded late onset EPs, because the large EP amplitude declined rapidly with faster stimulation rates and also with greater number of averaging, and the sensation threshold was very unstable, all different to somatosensory EPs.     

Spinal GABA(A) receptors do not mediate the sympathetic baroreceptor reflex in the rat

Activation of baroreceptors causes efferent sympathetic nerve activity (SNA) to fall. Two mechanisms could account for this sympathoinhibition: disfacilitation of sympathetic preganglionic neurons (SPN) and/or direct inhibition of SPN. The roles that spinal GABA and glycine receptors play in the baroreceptor reflex were examined in anesthetized, paralyzed, and artificially ventilated rats. Spinal GABA(A) receptors were blocked by an intrathecal injection of bicuculline methiodide, whereas glycine receptors were blocked with strychnine. Baroreceptors were activated by stimulation of the aortic depressor nerve (ADN), and a somatosympathetic reflex was used as control. After an intrathecal injection of vehicle, there was no effect on any measured variable or evoked reflex. In contrast, bicuculline caused a dose-dependent increase in arterial pressure, SNA, phrenic nerve discharge, and it significantly facilitated the somatosympathetic reflex. However, bicuculline did not attenuate either the depressor response or sympathoinhibition evoked after ADN stimulation. Similarly, strychnine did not affect the baroreceptor-induced depressor response. Thus GABA(A) and glycine receptors in the spinal cord have no significant role in baroreceptor-mediated sympathoinhibition.     

Transient receptor potential A1 channel contributes to activation of the muscle reflex

This study was undertaken to elucidate the role played by transient receptor potential A1 channels (TRPA1) in activating the muscle reflex, a sympathoexcitatory drive originating in contracting muscle. First, we tested the hypothesis that stimulation of the TRPA1 located on muscle afferents reflexly increases sympathetic nerve activity. In decerebrate rats, allyl isothiocyanate, a TRPA1 agonist, was injected intra-arterially into the hindlimb muscle circulation. This led to a 33% increase in renal sympathetic nerve activity (RSNA). The effect of allyl isothiocyanate was a reflex because the response was prevented by sectioning the sciatic nerve. Second, we tested the hypothesis that blockade of TRPA1 reduces RSNA response to contraction. Thirty-second continuous static contraction of the hindlimb muscles, induced by electrical stimulation of the peripheral cut ends of L(4) and L(5) ventral roots, increased RSNA and blood pressure. The integrated RSNA during contraction was reduced by HC-030031, a TRPA1 antagonist, injected intra-arterially (163 ± 24 vs. 95 ± 21 arbitrary units, before vs. after HC-030031, P < 0.05). Third, we attempted to identify potential endogenous stimulants of TRPA1, responsible for activating the muscle reflex. Increases in RSNA in response to injection into the muscle circulation of arachidonic acid, bradykinin, and diprotonated phosphate, which are metabolic by-products of contraction and stimulants of muscle afferents during contraction, were reduced by HC-030031. These observations suggest that the TRPA1 located on muscle afferents is part of the muscle reflex and further support the notion that arachidonic acid metabolites, bradykinin, and diprotonated phosphate are candidates for endogenous agonists of TRPA1.     

The role of reflex mechanisms in postinhibitory rebound studied by analysis of human single motor unit activity

The mechanism of onset of rebound after inhibition induced by electrical stimulation of a nerve of maximal and submaximal strength for M-response was studied in single motor units of normal human soleus, rectus femoris, and hand muscles. Poststimulus histograms and changes in the duration of interspike intervals were compared with mechanical recordings of muscle contractions. In all muscles tested, during strong isotonic contraction, the increase in motor unit activity after a silent period was partly due to synchronization of their emergence from inhibition. However, it also contained a component of true facilitation of motoneurons, which was evidently a reflex response to lengthening of the muscle in the relaxation phase after evoked contraction. The latent period of this facilitation in the soleus and rectus femoris muscles coincided in value with the latent period of the monosynaptic spinal reflex, whereas in the hand muscles, in which a monosynaptic response to electrical nerve stimulation could not be evoked, the latent period of facilitation as a result of spindle activation during muscle relaxation was significantly longer than the latent period of the monosynaptic reflex. These findings support the hypothesis of presynaptic suppression of monosynaptic connections of Ia afferents with the motoneurons of some human muscles by descending tonic influences and of the use of information coming from spindles by supraspinal levels of the CNS.     

Modeling the spinal pudendo-vesical reflex for bladder control by pudendal afferent stimulation

Electrical stimulation of the pudendal nerve (PN) is a promising approach to restore continence and micturition following bladder dysfunction resulting from neurological disease or injury. Although the pudendo-vesical reflex and its physiological properties are well established, there is limited understanding of the specific neural mechanisms that mediate this reflex. We sought to develop a computational model of the spinal neural network that governs the reflex bladder response to PN stimulation. We implemented and validated a neural network architecture based on previous neuroanatomical and electrophysiological studies. Using synaptically-connected integrate and fire model neurons, we created a network model with realistic spiking behavior. The model produced expected sacral parasympathetic nucleus (SPN) neuron firing rates from prescribed neural inputs and predicted bladder activation and inhibition with different frequencies of pudendal afferent stimulation. In addition, the model matched experimental results from previous studies of temporal patterns of pudendal afferent stimulation and selective pharmacological blockade of inhibitory neurons. The frequency- and pattern-dependent effects of pudendal afferent stimulation were determined by changes in firing rate of spinal interneurons, suggesting that neural network interactions at the lumbosacral level can mediate the bladder response to different frequencies or temporal patterns of pudendal afferent stimulation. Further, the anatomical structure of excitatory and inhibitory interneurons in the network model was necessary and sufficient to reproduce the critical features of the pudendo-vesical reflex, and this model may prove useful to guide development of novel, more effective electrical stimulation techniques for bladder control.     

Thin-fiber mechanoreceptors reflexly increase renal sympathetic nerve activity during static contraction

The renal vasoconstriction induced by the sympathetic outflow during exercise serves to direct blood flow from the kidney toward the exercising muscles. The renal circulation seems to be particularly important in this regard, because it receives a substantial part of the cardiac output, which in resting humans has been estimated to be 20%. The role of group III mechanoreceptors in causing the reflex renal sympathetic response to static contraction remains an open question. To shed some light on this question, we recorded the renal sympathetic nerve responses to static contraction before and after injection of gadolinium into the arterial supply of the statically contracting triceps surae muscles of decerebrate unanesthetized and chloralose-anesthetized cats. Gadolinium has been shown to be a selective blocker of mechanogated channels in thin-fiber muscle afferents, which comprise the afferent arm of the exercise pressor reflex arc. In decerebrate (n = 15) and chloralose-anesthetized (n = 12) cats, we found that gadolinium (10 mM; 1 ml) significantly attenuated the renal sympathetic nerve and pressor responses to static contraction (60 s) after a latent period of 60 min; both responses recovered after a latent period of 120 min. We conclude that thin-fiber mechanoreceptors supplying contracting muscle are involved in some of the renal vasoconstriction evoked by the exercise pressor reflex.     

A 5-HT4 agonist mosapride enhances rectorectal and rectoanal reflexes in guinea pigs

The rectal distension-evoked reflex rectal (R-R) contractions and internal anal sphincter (R-IAS) relaxations in guinea pigs were generated through the extrinsic sacral excitatory nerve pathway (pelvic nerves) and the intrinsic cholinergic excitatory and nitrergic inhibitory nerve pathways. The aim of the present study was to evaluate whether a prokinetic benzamide, mosapride, enhances the R-R and R-IAS reflexes mediated via 5-HT4 receptors in the guinea pig. The mechanical activities of the R and IAS were recorded with a balloon connected to a pressure transducer and a strain gauge force transducer in the anesthetized guinea pig with intact spinal-intestinal pathways. Gradual and sustained rectal distension evoked R-R contractions and synchronous R-IAS relaxations. Mosapride (0.1-1.0 mg/kg i.v.) dose-dependently enhanced both R-R and R-IAS reflex responses. Reflex indexes for R-R and R-IAS maximally increased from 1.0 (control) to 1.92 and 1.88, respectively. A specific 5-HT4 receptor antagonist, GR 113808 (1.0 mg/kg i.v.), antagonized the enhancement of the R-R and R-IAS reflexes induced by mosapride 1.0 mg/kg i.v. The present results indicate that mosapride enhanced the R-R and R-IAS reflexes mediated through 5-HT4 receptors.