Impaired Regulation of Submaximal Force after ACL Reconstruction: Role of Muscle Spindles.

Ongoing motor deficits are routinely present following anterior cruciate ligament (ACL) reconstruction, including the ability to regulate muscle force. While such deficits are known, it is unclear why this occurs. The goal of the current study was to investigate the potential influence of muscle spindle input on submaximal force regulation and muscle activity at the knee in people following ACL reconstruction. Fourteen participants (8 female) who were 6-24 months post-ACL reconstruction and 15 control participants (8 female) undertook submaximal force matching and force modulation tasks before and after 20 min of vibration applied to the patella tendon. Across all tasks, the ACL reconstruction participants were poorer at force matching (P=0.007). The effect of vibration was not significant in either group for the force matching tasks (P=0.06), although there was a reduction in maximum voluntary contraction post-vibration in the control group (P<0.001). The ACL reconstruction group also showed evidence of greater activation of the medial hamstring muscles in comparison to controls (P=0.04). Individuals who have undergone ACL reconstruction have a diminished ability to accurately match and regulate submaximal muscle force, but this does not appear to be related to impaired muscle spindle input. Neuromuscular retraining programs that involve force regulation tasks may be necessary to optimize rehabilitation after ACL reconstruction.

Relationship between muscle spindles and myofascial trigger spots according to Hoffmann reflex pathway and tissue morphology characteristics in a rat model.

OBJECTIVES: To determine how muscle spindles are involved in the pathophysiology of chronic myofascial trigger spots (MTrSs, similar to myofascial trigger points) in a rat injury model according to the characteristics of the Hoffmann reflex (H-reflex) and the anatomical relationship between muscle spindles and MTrSs. METHODS: 16 male Sprague-Dawley rats (7 weeks old) were randomly divided into experimental and control groups. A blunt strike injury and eccentric exercise were applied to the gastrocnemius muscle of rats in the experimental group once a week for 8 weeks as a MTrS modelling intervention. Subsequently, the rats were reared normally and rested for 4 weeks. At the end of the 12th week, the rats were examined for the presence of MTrSs defined by the detection of a palpable taut band exhibiting both a local twitch response and spontaneous electrical activity. After modelling, evocation of the H-reflex and morphological examination of muscle spindles and MTrSs were conducted. RESULTS: The threshold (0.35±0.04 mA) of the H-reflex and latency (1.24±0.18 ms) of the M wave recorded at MTrSs were not significantly different to those at non-MTrSs (P>0.05). Compared with non-MTrSs, a lower Mmax (4.28±1.27 mV), higher Hmax (median (IQR) 0.95 (0.80-1.08) mV) and Hmax/Mmax (median (IQR) 0.21 (0.16-0.40)), and shorter H wave latency (4.60±0.89 ms) were recorded at MTrSs (P<0.05). Morphologically, there was a close anatomical relationship between the MTrS cells and the muscle spindles. DISCUSSION: Compared with normal muscles, the H-reflex myoelectrical activity was enhanced and some muscle spindles might have been influenced by active MTrSs. Thus, muscle spindles may play an important role in the pathological mechanism underlying myofascial trigger points.

Diet-induced obesity decreases rate-dependent depression in the Hoffmann's reflex in adult mice.

Obesity is associated with balance and motor control deficits. We have recently shown that Group Ia muscle spindle afferents, the sensory arm of the muscle stretch reflex, are less responsive in mice fed a high-fat diet. Here we test the hypothesis that reflex excitability to sensory information from Group Ia muscle spindle afferents is altered in a mouse model of diet-induced obesity. We measured the anesthetized Hoffmann's or H-reflex, the electrical analog of the muscle stretch reflex. Adult mice of both sexes were fed a control diet (CD; 10% kcal from fat) or a high-fat diet (HFD; 60% kcal from fat) for 5, 10, or 15 weeks. We used three quantitative measures of H-reflex excitability: (1) H-reflex latency; (2) the percentage of motor neurons recruited from electrical stimulation of Group Ia muscle spindle afferents (Hmax /Mmax ); and (3) rate-dependent depression (RDD), the decrease in H-reflex amplitude to high frequency stimulation (20 stimuli at 5 Hz). A HFD did not significantly alter H latency (P = 0.16) or Hmax /Mmax ratios (P = 0.06), but RDD was significantly lower in HFD compared to CD groups (P < 0.001). Interestingly, HFD males exhibited decreased RDD compared to controls only after 5 and 10 weeks of feeding, but females showed progressive decreases in RDD that were only significant at 10 and 15 weeks on the HFD. These results suggest that high-fat feeding increases H-reflex excitability. Future studies are needed to determine whether these changes alter muscle stretch reflex strength and/or balance and to determine the underlying mechanism(s).

Effects of tonic muscle pain on fusimotor control of human muscle spindles during isometric ankle dorsiflexion.

Studies on anesthetized animals have revealed that nociceptors can excite fusimotor neurons and thereby change the sensitivity of muscle spindles to stretch; such nociceptive reflexes have been suggested to underlie the mechanisms that lead to chronic musculoskeletal pain syndromes. However, the validity of the "vicious cycle" hypothesis in humans has yielded results contrasting with those found in animals. Given that spindle firing rates are much lower in humans than in animals, it is possible that some of the discrepancies between human experimental data and those obtained in animals could be explained by differences in background fusimotor drive when the leg muscles are relaxed. We examined the effects of tonic muscle pain during voluntary contractions of the ankle dorsiflexors. Unitary recordings were obtained from 10 fusimotor-driven muscle spindle afferents (6 primary, 4 secondary) supplying the ankle dorsiflexors via a microelectrode inserted percutaneously into the common peroneal nerve. A series of 1-min weak contractions was performed at rest and during 1 h of muscle pain induced by intramuscular infusion of 5% hypertonic saline into the tibialis anterior muscle. We did not observe any statistically significant increases in muscle spindle firing rates of six afferents followed during tonic muscle pain, although discharge variability increased slightly. Furthermore, a participant's capacity to maintain a constant level of force, while relying on proprioceptive feedback in the absence of visual feedback, was not compromised during pain. We conclude that nociceptive inputs from contracting muscle do not excite fusimotor neurons during voluntary isometric contractions in humans. NEW & NOTEWORTHY Data obtained in the cat have shown that muscle pain causes a marked increase in the firing of muscle spindles, attributed to a nociceptor-driven fusimotor reflex. However, our studies of muscle spindles in relaxed leg muscles failed to find any effect on spindle discharge. Here we showed that experimental muscle pain failed to increase the firing of muscle spindle afferents during weak voluntary contractions, when fusimotor drive sufficient to increase their firing is present.

Impaired sensorimotor control of the hand in congenital absence of functional muscle spindles.

Patients with hereditary sensory and autonomic neuropathy type III (HSAN III) exhibit marked ataxia, including gait disturbances. We recently showed that functional muscle spindle afferents in the leg, recorded via intraneural microelectrodes inserted into the peroneal nerve, are absent in HSAN III, although large-diameter cutaneous afferents are intact. Moreover, there is a tight correlation between loss of proprioceptive acuity at the knee and the severity of gait impairment. We tested the hypothesis that manual motor performance is also compromised in HSAN III, attributed to the predicted absence of muscle spindles in the intrinsic muscles of the hand. Manual performance in the Purdue pegboard task was assessed in 12 individuals with HSAN III and 11 age-matched healthy controls. The mean (±SD) pegboard score (number of pins inserted in 30 s) was 8.1 ± 1.9 and 8.6 ± 1.8 for the left and right hand, respectively, significantly lower than the scores for the controls (15.0 ± 1.3 and 16.0 ± 1.1; P < 0.0001). Performance was not improved after kinesiology tape was applied over the joints of the hand. In 5 patients we inserted a tungsten microelectrode into the ulnar nerve at the wrist. No spontaneous or stretch-evoked muscle afferent activity could be identified in any of the 11 fascicles supplying intrinsic muscles of the hand, whereas touch-evoked activity from low-threshold cutaneous mechanoreceptor afferents could readily be recorded from 4 cutaneous fascicles. We conclude that functional muscle spindles are absent in the short muscles of the hand and most likely absent in the long finger flexors and extensors, and that this largely accounts for the poor manual motor performance in HSAN III. NEW & NOTEWORTHY We describe the impaired manual motor performance in patients with hereditary sensory and autonomic neuropathy type III (Riley-Day syndrome), who exhibit congenital insensitivity to pain, poor proprioception, and marked gait ataxia. We show that functional muscle spindles are absent in the intrinsic muscles of the hand, which we argue contributes to their poor performance in a task involving the precision grip.

Proprioception 2.0: novel functions for muscle spindles.

PURPOSE OF REVIEW: Muscle spindles are encapsulated mechanosensory receptors within skeletal muscle tissue that inform the central nervous system about the contractile status of each muscle. This information is required for any coordinated movement and for stable posture. This review summarizes recent findings regarding novel functions for proprioceptive feedback information, muscle spindle disease and the molecular basis of mechanoreception. RECENT FINDINGS: Muscle spindle function is not limited to regulating motor control but is also required for appropriate realignment of fractured bones, successful regeneration of spinal cord axons after injury and spinal alignment. Several proteins responsible for or modulating mechanotransduction in proprioceptive sensory neurons have been identified, including the Piezo2 channel as a candidate for the principal mechanotransduction channel. Many neuromuscular diseases are known to be accompanied by an impaired function of muscle spindles, resulting in a decline of motor performance and coordination in the patients. SUMMARY: Our knowledge regarding the molecular basis of muscle spindle function is still incomplete. However, increasing our understanding of mechanotransduction in muscle spindles is a prerequisite for finding appropriate strategies to prevent injuries due to unstable gait and frequent falls.

Diet induced obesity alters muscle spindle afferent function in adult mice.

Populations with obesity are more likely to fall and exhibit balance instability. The reason for this is likely multifactorial, but there is some evidence that sensory function is impaired during obesity. We tested the hypothesis that muscle proprioceptor function is compromised in a mouse model of diet induced obesity. An in vitro muscle-nerve preparation was used to record muscle spindle afferent responses to physiological stretch and sinusoidal vibration. We compared the responses of C57/Bl6 male and female mice on a control diet (10% kcal fat) with those eating a high fat diet (HFD; 60% kcal fat) for 10 weeks (final age 14-15 weeks old). Following HFD feeding, adult mice of both sexes exhibited decreased muscle spindle afferent responses to muscle movement. Muscle spindle afferent firing rates during the plateau phase of stretch were significantly lower in both male and female HFD animals as were two measures of dynamic sensitivity (dynamic peak and dynamic index). Muscle spindle afferents in male mice on a HFD were also significantly less likely to entrain to vibration. Due to the importance of muscle spindle afferents to proprioception and motor control, decreased muscle spindle afferent responsiveness may contribute to balance instability during obesity.

The Effect of Functional Mandibular Shift on the Muscle Spindle Systems in Head-Neck Muscles and the Related Neurotransmitter Histamine.

The aim of this study is to explore the effects of abnormal occlusion and functional recovery caused by functional mandible deviation on the head and neck muscles and muscle spindle sensory-motor system by electrophysiological response and endogenous monoamine neurotransmitters' distribution in the nucleus of the spinal tract. Seven-week-old male Wistar rats were randomly divided into 7 groups: normal control group, 2W experimental control group, 2W functional mandible deviation group, 2W functional mandible deviation recovery group, 4W experimental control group, 4W functional mandible deviation group, 4W functional mandible deviation recovery group. Chewing muscles, digastric muscle, splenius, and trapezius muscle spindles electrophysiological response activities at the opening and closing state were recorded. And then the chewing muscles, digastric, splenius, trapezius, and neck trigeminal nucleus were taken for histidine decarboxylase (HDC) detection by high performance liquid chromatography (HPLC), immunofluorescence, and reverse-transcription polymerase chain reaction (RT-PCR). Histamine receptor proteins in the neck nucleus of the spinal tract were also examined by immunofluorescence and RT-PCR. Electromyography activity of chewing muscles, digastric, and splenius muscle was significantly asymmetric; the abnormal muscle electromyography activity was mainly detected at the ipsilateral side. After functional mandibular deviation, muscle sensitivity on the ipsilateral sides of the chewing muscle and splenius decreased, muscle excitement weakened, modulation depth decreased, and the muscle spindle afferent impulses of excitation transmission speed slowed down. Changes for digastric muscle electrical activity were contrary. The functions recovered at different extents after removing the deflector. However, trapezius in all the experimental groups and recovery groups exhibited bilateral symmetry electrophysiological responses, and no significant difference compared with the control group. After functional mandibular deviation, HDC protein and messenger ribonucleic acid (mRNA) levels on the ipsilateral sides of the chewing muscle and splenius increased significantly. HDC level changes for digastric muscle were contrary. After the removal of the mandibular position deflector, HDC protein and mRNA levels decreased on the ipsilateral sides of the chewing muscle and splenius while they increased in the digastric muscle. The difference of histamine decarboxylase content in the bilateral trapezius in each experimental group was small. After functional mandibular deviation, the temporomandibular joint mechanical receptors not only caused the fusimotor fiber hypoallergenic fatigue slow response on the ipsilateral sides of splenius, but also increased the injury neurotransmitter histamine release. The authors' results further support the opinion that the temporomandibular joint receptors may be involved in the mechanical theory of the head and neck muscles nervous system regulation.

Muscle spindle alterations precede onset of sensorimotor deficits in Charcot-Marie-Tooth type 2E.

Charcot-Marie-Tooth (CMT) is the most common inherited peripheral neuropathy, affecting approximately 2.8 million people. The CMT leads to distal neuropathy that is characterized by reduced motor nerve conduction velocity, ataxia, muscle atrophy and sensory loss. We generated a mouse model of CMT type 2E (CMT2E) expressing human neurofilament light E396K (hNF-LE396K ), which develops decreased motor nerve conduction velocity, ataxia and muscle atrophy by 4 months of age. Symptomatic hNF-LE396K mice developed phenotypes that were consistent with proprioceptive sensory defects as well as reduced sensitivity to mechanical stimulation, while thermal sensitivity and auditory brainstem responses were unaltered. Progression from presymptomatic to symptomatic included a 50% loss of large diameter sensory axons within the fifth lumbar dorsal root of hNF-LE396K mice. Owing to proprioceptive deficits and loss of large diameter sensory axons, we analyzed muscle spindle morphology in presymptomatic and symptomatic hNF-LE396K and hNF-L control mice. Muscle spindle cross-sectional area and volume were reduced in all hNF-LE396K mice analyzed, suggesting that alterations in muscle spindle morphology occurred prior to the onset of typical CMT pathology. These data suggested that CMT2E pathology initiated in the muscle spindles altering the proprioceptive sensory system. Early sensory pathology in CMT2E could provide a unifying hypothesis for the convergence of pathology observed in CMT.

Absent quadriceps reflex with distant toe flexor response: An underrecognized neurological sign.

As opposed to finger flexion response upon tapping the styloid process with absent brachioradialis reflex (inverted brachioradialis reflex), toe flexion response upon patellar percussion with absent quadriceps reflex is a quite underrecognized neurological sign, and has been reported only once in the literature. Similar to the inverted brachioradialis reflex, this sign can also be useful for neurological localization. We hereby report a patient presenting with signs and symptoms of lumbar radiculopathy in the setting of an anterior epidural mass compressing the cauda equina at L2-L4, without evidence of myelopathy. Upon examination, the patient had bilateral absent quadriceps reflexes with a right toe flexor response when the right patella was percussed. An absent quadriceps reflex with distant toe flexor response is proposed as a lower extremity equivalent of the inverted brachioradialis reflex, likely localizing to L3-L4 levels. Spindle hypersensitivity due to lack of reciprocal inhibition from antagonist muscles is hypothesized as a possible underlying mechanism. Further observations should help clarify the most common underlying etiology (radicular vs. radiculomyelopathy). Neurologists should be able to recognize this sign, as it can be helpful for neurological localization.

Oblicuidad pélvica o contractura congénita en abducción de la cadera: una entidad poco conocida / Congenital pelvic obliquity or congenital hip’s abduction contracture: a little known entity

La oblicuidad pélvica congénita es una patología frecuente en el lactante y poco conocida por los pediatras. Se presentan cuatro casos de oblicuidad pélvica simple en lactantes mujeres. Se describen los hallazgos clínicos y radiológicos en el momento del diagnóstico, la actitud terapéutica y la evolución de cada uno de ellos. Los pediatras de Atención Primaria debemos estar atentos a los antecedentes, signos acompañantes y al diagnóstico de esta entidad, así como tener formación en la exploración de la cadera para detectar clínicamente una inestabilidad, preferentemente en la cadera aducta (opuesta a la contracturada). Es importante la interrelación entre Pediatría, Radiología Infantil, Traumatología Infantil y Rehabilitación (AU)

Congenital pelvic obliquity is frequent, although pediatricians are not used to diagnose it. We report four female infants with simple pelvic obliquity. We describe clinical and radiologic findings, their treatment and outcome. Primary care pediatricians must be alert looking for pelvic obliquity in infants. We need to improve our abilities in hip exploration, to detect instability in the adduct hip (in the opposite of the contractured hip). Is very important to work together: pediatricians, radiologist, orthopedist and rehabilitation physician (AU)

[The evaluation of hyperkineses in hepatocerebral dystrophy (Wilson-Konovalov disease) from the position of the theory of muscle spindles].

OBJECTIVE: To obtain evidence for the possibility of considering hyperkineses in hepatocerebtal dystrophy from the position of the theory of muscle spindles. MATERIAL AND METHODS: We examined 27 patients: rigid-arrhythmic-hyperkinetic form was diagnosed in 2 patients, trembling-rigid in 8, trembling in 16 and extrapyramidal-cortical in 1. Electromyography of different muscles in resting state and functional loadings taking into account surgical intervention was the main method of the study. RESULTS AND CONCLUSION: An analysis of electrophysiological results based on hyperkinesis variant (torsion dystonic, choreoathetoid etc) revealed a role of the striatal pallidal system in the anomalous control of static and dynamic γ-motorneurons and involvement of spinal reflexes in forced movements. This hypothesis may help to deeply understand the genesis of extrapyramidal dyskinesia and more reasonably select a stereotaxic target in surgical treatment.

Stretch Evoked Potentials in Healthy Subjects and After Stroke: A Potential Measure for Proprioceptive Sensorimotor Function.

Sensory feedback is of vital importance in motor control, yet rarely assessed in diseases with impaired motor function like stroke. Muscle stretch evoked potentials (StrEPs) may serve as a measure of cortical sensorimotor activation in response to proprioceptive input. The aim of this study is: 1) to determine early and late features of the StrEP and 2) to explore whether StrEP waveform and features can be measured after stroke. Consistency of StrEP waveforms and features was evaluated in 22 normal subjects. StrEP features and similarity between hemispheres were evaluated in eight subacute stroke subjects. StrEPs of normal subjects had a consistent shape across conditions and sessions (mean cross correlation waveforms > 0.75). Stroke subjects showed heterogeneous StrEP waveforms. Stroke subjects presented a normal early peak (40 ms after movement onset) but later peaks had abnormal amplitudes and latencies. No significant differences between stroke subjects with good and poor motor function were found (P > 0.14). With the consistent responses of normal subjects the StrEP meets a prerequisite for potential clinical value. Recording of StrEPs is feasible even in subacute stroke survivors with poor motor function. How StrEP features relate to clinical phenotypes and recovery needs further investigation.

The role of gap junctions in stretch-induced atrial fibrillation.

AIMS: The aim of this study was to investigate the role of gap junctions in atrial fibrillation (AF) by analysing the effects of a gap junction enhancer and blocker on AF vulnerability and electrophysiological properties of isolated hearts. METHODS AND RESULTS: The acute atrial stretch model of AF in the isolated rabbit heart was used. Sustained AF (SAF) was induced by a burst of high-frequency stimulation of the Bachmann's bundle. The effective refractory period (ERP) was measured, and the total conduction time (TCT) and the pattern of conduction of the anterior surface of the left atrium were monitored by using an optical mapping system. The effect of enhancing gap junction function by 100-1000 nM rotigaptide (ZP123) and block by 30 µM carbenoxolone on these parameters was measured. SAF inducibility was increased with an elevation of intra-atrial pressure. Enhanced gap junction conductance induced by treatment with 100-1000 nM rotigaptide reduced SAF inducibility, and the gap junction blocker carbenoxolone increased SAF inducibility. In the absence of gap junction enhancer or blocker, normal conduction was observed at 0 cmH2O. When intra-atrial pressure was raised to 12 cmH2O, the conduction pattern was changed to a heterogeneous zig-zag pattern and TCT was prolonged. Conduction pattern was not affected by either agent. Rotigaptide shortened TCT, whereas carbenoxolone prolonged TCT. ERP was significantly shortened with an increase in intra-atrial pressure, but ERP was unaffected by either agent. CONCLUSION: Gap junction modulators changed AF inducibility through their effects on atrial conduction, not by altering ERP.

Hereditary motor and sensory neuropathy with proximal predominance (HMSN-P).

Hereditary motor and sensory neuropathy with proximal predominance (HMSN-P) is a rare disorder inherited in an autosomal dominant fashion. Patients present with slowly progressive proximal-predominant weakness, painful muscle cramps, fasciculations, large-fiber sensory loss, and areflexia. Electrodiagnostic (EDX) studies typically reveal abnormalities consistent with a sensorimotor neuronopathy. A patient with HMSN-P underwent EDX studies, revealing ongoing and chronic neurogenic denervation, motor unit instability, and neuromyotonic discharges, further defining the spectrum of EDX findings in HMSN-P. The clinical, pathological, and genetic features are also reviewed. The appearance of HMSN-P in the United States and elsewhere calls for clinicians in nonendemic regions to be familiar with this rare disorder, which has typically been geographically confined.

Muscle spindle traffic in functionally unstable ankles during ligamentous stress.

CONTEXT: Ankle sprains are common in athletes, with functional ankle instability (FAI) developing in approximately half of cases. The relationship between laxity and FAI has been inconclusive, suggesting that instability may be caused by insufficient sensorimotor function and dynamic restraint. Research has suggested that deafferentation of peripheral mechanoreceptors potentially causes FAI; however, direct evidence confirming peripheral sensory deficits has been elusive because previous investigators relied upon subjective proprioceptive tests. OBJECTIVE: To develop a method for simultaneously recording peripheral sensory traffic, joint forces, and laxity and to quantify differences between healthy ankles and those with reported instability. DESIGN: Case-control study. SETTING: University laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 29 participants (age = 20.9 ± 2.2 years, height = 173.1 ± 8.9 cm, mass = 74.5 ± 12.7 kg) stratified as having healthy (HA, n = 19) or unstable ankles (UA, n = 10). INTERVENTION(S): Sensory traffic from muscle spindle afferents in the peroneal nerve was recorded with microneurography while anterior (AP) and inversion (IE) stress was applied to ligamentous structures using an ankle arthrometer under test and sham conditions. MAIN OUTCOME MEASURE(S): Laxity (millimeters or degrees) and amplitude of sensory traffic (percentage) were determined at 0, 30, 60, 90, and 125 N of AP force and at 0, 1, 2, 3, and 4 Nm of IE torque. Two-factor repeated-measures analyses of variance were used to determine differences between groups and conditions. RESULTS: No differences in laxity were observed between groups (P > .05). Afferent traffic increased with increased force and torque in test trials (P < .001). The UA group displayed decreased afferent activity at 30 N of AP force compared with the HA group (HA: 30.2% ± 9.9%, UA: 17.1% ± 16.1%, P < .05). CONCLUSIONS: The amplitude of sensory traffic increased simultaneously with greater ankle motion and loading, providing evidence of the integrated role of capsuloligamentous and musculotendinous mechanoreceptors in maintaining joint sensation. Unstable ankles demonstrated diminished afferent traffic at low levels of force, suggesting the early detection of joint loading may be compromised.

[Relationship between simulated weightlessness-induced muscle spindle change and muscle atrophy].

One of the most important and urgent issues in the field of space medicine is to reveal the potential mechanism underlying the disused muscle atrophy during the weightlessness or microgravity environment. It will conduce to find out effective methods for the prevention and treatment of muscle atrophy during a long-term space flight. Increasing data show that muscle spindle discharges are significantly altered following the hindlimb unloading, suggesting a vital role in the progress of muscle atrophy. In the last decades, we have made a series of studies on changes in the morphological structure and function of muscle spindle following simulated weightlessness. This review will discuss our main results and related researches for understanding of muscle spindle activities during microgravity environment, which may provide a theoretic basis for effective prevention and treatment of muscle atrophy induced by weightlessness.

Bradykinin B2 receptor contributes to the exaggerated muscle mechanoreflex in rats with femoral artery occlusion.

Static muscle contraction activates the exercise pressor reflex, which in turn increases sympathetic nerve activity (SNA) and blood pressure (BP). Bradykinin (BK) is considered as a muscle metabolite responsible for modulation of the sympathetic and cardiovascular responses to muscle contraction. Prior studies have suggested that kinin B2 receptor mediates the effects of BK on the reflex SNA and BP responses during stimulation of skeletal muscle afferents. In patients with peripheral artery disease and a rat model with femoral artery ligation, amplified SNA and BP responses to static exercise were observed. This dysfunction of the exercise pressor reflex has previously been shown to be mediated, in part, by muscle mechanoreflex overactivity. Thus, in this report, we determined whether kinin B2 receptor contributes to the augmented mechanoreflex activity in rats with 24 h of femoral artery occlusion. First, Western blot analysis was used to examine protein expression of B2 receptors in dorsal root ganglion tissues of control limbs and ligated limbs. Our data show that B2 receptor displays significant overexpression in ligated limbs as compared with control limbs (optical density: 0.94 ± 0.02 in control and 1.87 ± 0.08 after ligation, P < 0.05 vs. control; n = 6 in each group). Second, mechanoreflex was evoked by muscle stretch and the reflex renal SNA (RSNA) and mean arterial pressure (MAP) responses to muscle stretch were examined after HOE-140, a B2 receptors blocker, was injected into the arterial blood supply of the hindlimb muscles. The results demonstrate that the stretch-evoked reflex responses were attenuated by administration of HOE-140 in control rats and ligated rats; however, the attenuating effects of HOE-140 were significantly greater in ligated rats, i.e., after 5 µg/kg of HOE-140 RSNA and MAP responses evoked by 0.5 kg of muscle tension were attenuated by 43% and 25% in control vs. 54% and 34% in ligation (P < 0.05 vs. control group; n = 11 in each group). In contrast, there was no significant difference in B1 receptor expression in both experimental groups, and arterial injection of R-715, a B1 receptors blocker, had no significant effects on RSNA and MAP responses evoked by muscle stretch. Accordingly, results obtained from this study support our hypothesis that heightened kinin B2 receptor expression in the sensory nerves contributes to the exaggerated muscle mechanoreflex in rats with femoral artery occlusion.

Differential effect of central command on aortic and carotid sinus baroreceptor-heart rate reflexes at the onset of spontaneous, fictive motor activity.

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in conscious cats and spontaneous contraction in decerebrate cats. The purpose of this study was to examine whether central command attenuates the sensitivity of the carotid sinus baroreceptor-HR reflex at the onset of spontaneous, fictive motor activity in paralyzed, decerebrate cats. We confirmed that aortic nerve (AN)-stimulation-induced bradycardia was markedly blunted to 26 ± 4.4% of the control (21 ± 1.3 beats/min) at the onset of spontaneous motor activity. Although the baroreflex bradycardia by electrical stimulation of the carotid sinus nerve (CSN) was suppressed (P < 0.05) to 86 ± 5.6% of the control (38 ± 1.2 beats/min), the inhibitory effect of spontaneous motor activity was much weaker (P < 0.05) with CSN stimulation than with AN stimulation. The baroreflex bradycardia elicited by brief occlusion of the abdominal aorta was blunted to 36% of the control (36 ± 1.6 beats/min) during spontaneous motor activity, suggesting that central command is able to inhibit the cardiomotor sensitivity of arterial baroreflexes as the net effect. Mechanical stretch of the triceps surae muscle never affected the baroreflex bradycardia elicited by AN or CSN stimulation and by aortic occlusion, suggesting that muscle mechanoreflex did not modify the cardiomotor sensitivity of aortic and carotid sinus baroreflex. Since the inhibitory effect of central command on the carotid baroreflex pathway, associated with spontaneous motor activity, was much weaker compared with the aortic baroreflex pathway, it is concluded that central command does not force a generalized modulation on the whole pathways of arterial baroreflexes but provides selective inhibition for the cardiomotor component of the aortic baroreflex.

A role for nitric oxide within the nucleus tractus solitarii in the development of muscle mechanoreflex dysfunction in hypertension.

Evidence suggests that the muscle mechanoreflex, a circulatory reflex that raises blood pressure and heart rate (HR) upon activation of mechanically sensitive afferent fibres in skeletal muscle, is overactive in hypertension. However, the mechanisms underlying this abnormal reflex function have yet to be identified. Sensory input from the mechanoreflex is processed within the nucleus tractus solitarii (NTS) in the medulla oblongata. Within the NTS, the enzymatic activity of nitric oxide synthase produces nitric oxide (NO). This centrally derived NO has been shown to modulate muscle reflex activity and serves as a viable candidate for mediating the mechanoreflex dysfunction that develops in hypertension. We hypothesized that mechanoreflex dysfunction in hypertension is mediated by abnormal alterations in NO production in the NTS. Mechanically sensitive afferent fibres were stimulated by passively stretching hindlimb muscle before and after blocking the endogenous production of NO within the NTS via microdialysis of the NO synthase inhibitor L-NAME (1 and 5 mM) in normotensive Wistar-Kyoto rats and spontaneously hypertensive rats (SHRs). Changes in HR and mean arterial pressure in response to stretch were significantly larger in SHRs compared with Wistar-Kyoto rats prior to L-NAME dialysis. Attenuating NO production via L-NAME in normotensive rats recapitulated the exaggerated cardiovascular response to stretch observed in SHRs. Dialysing L-NAME in SHRs further accentuated the increases in HR and mean arterial pressure elicited by stretch. These findings support the contention that reductions in NO production within the NTS contribute to the generation of abnormal cardiovascular control by the skeletal muscle mechanoreflex in hypertension.