Possible contributions of CPG activity to the control of rhythmic human arm movement

There is extensive modulation of cutaneous and H-reflexes during rhythmic leg movement in humans. Mechanisms controlling reflex modulation (e.g., phase- and task-dependent modulation, and reflex reversal) during leg movements have been ascribed to the activity of spinal central pattern generating (CPG) networks and peripheral feedback. Our working hypothesis has been that neural mechanisms (i.e., CPGs) controlling rhythmic movement are conserved between the human lumbar and cervical spinal cord. Thus reflex modulation during rhythmic arm movement should be similar to that for rhythmic leg movement. This hypothesis has been tested by studying the regulation of reflexes in arm muscles during rhythmic arm cycling and treadmill walking. This paper reviews recent studies that have revealed that reflexes in arm muscles show modulation within the movement cycle (e.g., phase-dependency and reflex reversal) and between static and rhythmic motor tasks (e.g., task-dependency). It is concluded that reflexes are modulated similarly during rhythmic movement of the upper and lower limbs, suggesting similar motor control mechanisms. One notable exception to this pattern is a failure of contralateral arm movement to modulate reflex amplitude, which contrasts directly with observations from the leg. Overall, the data support the hypothesis that CPG activity contributes to the neural control of rhythmic arm movement.     

Circadian coupling between pancreatic secretion and intestinal motility in humans

Human interdigestive intestinal motility follows a circadian rhythm with reduced nocturnal activity, but circadian pancreatic exocrine secretion is unknown. To determine whether circadian changes in interdigestive pancreatic secretion occur and are associated with motor events, pancreatic enzyme outputs, proximal jejunal motility, and plasma pancreatic polypeptide concentrations were measured during consecutive daytime and nighttime periods (12 h each) in seven healthy volunteers using orojejunal multilumen intubation. Studies were randomly started in the morning or evening. Nocturnally, motility decreased (motor quiescence: 67 +/- 22 vs. 146 +/- 37 min; motility index: 3.59 +/- 0.33 vs. 2.78 +/- 0.40 mmHg/min; both P < 0.05) but amylase output increased (273 +/- 78 vs. 384 +/- 100 U/min; P < 0.05) and protease output remained unchanged (P > 0.05); consequently, enzyme/motility ratio increased. Amylase outputs were always lowest during phase I. Motor but not pancreatic circadian activities were associated with sleep. Pancreatic polypeptide plasma concentrations were unchanged. Consequently, intestinal motor and pancreatic exocrine functions may have different circadian rhythms, i.e., decreased motor and stable secretory activity during the night. However, the association between individual phases of interdigestive motor and secretory activity is preserved. The nocturnal increase in enzyme/motility ratio is probably not caused by increased cholinergic tone.     

Captopril attenuates reflex adrenergic response in essential hypertension

An attenuation of adrenergic activity during the inhibition of endogenous angiotensin II formation was evaluated by determining plasma norepinephrine concentration after a single oral administration of captopril compared to that after nifedipine in essential hypertension. Captopril produced a fall in mean arterial pressure (-24 +/- 2 mmHg, p less than 0.01) which magnitude was the same as that gained by nifedipine (-22 +/- 3 mmHg, p less than 0.01). Reflex tachycardia due to hypotension was produced (+13 +/- 1 beats/min, p less than 0.01) after nifedipine but not after captopril (-1 +/- 2 beats/min, p greater than 0.05). Although the enhancement of plasma renin activity induced by captopril (+1.54 +/- 0.56 ng/ml/hr, p less than 0.05) was similar (p greater than 0.05) to that by nifedipine (+1.44 +/- 0.47 ng/ml/hr, p less than 0.05), plasma norepinephrine concentration increased less (p less than 0.01) after captopril (+100 +/- 23 ng/ml, p less than 0.05) than after nifedipine (+283 +/- 51 ng/ml, p less than 0.05). Thus, the diminished adrenergic activity is a likely candidate for the abolished reflex tachycardia after the inhibition of angiotensin I converting enzyme activity by captopril in essential hypertension.     

Effect of thermal stress on the vestibulosympathetic reflexes in humans.

Both heat stress and vestibular activation alter autonomic responses; however, the interaction of these two sympathetic activators is unknown. To determine the effect of heat stress on the vestibulosympathetic reflex, eight subjects performed static head-down rotation (HDR) during normothermia and whole body heating. Muscle sympathetic nerve activity (MSNA; peroneal microneurography), mean arterial blood pressure (MAP), heart rate (HR), and internal temperature were measured during the experimental trials. HDR during normothermia caused a significant increase in MSNA (Delta5 +/- 1 bursts/min; Delta53 +/- 14 arbitrary units/min), whereas no change was observed in MAP, HR, or internal temperature. Whole body heating significantly increased internal temperature (Delta0.9 +/- 0.1 degrees C), MSNA (Delta10 +/- 3 bursts/min; Delta152 +/- 44 arbitrary units/min), and HR (Delta25 +/- 6 beats/min), but it did not alter MAP. HDR during whole body heating increased MSNA (Delta16 +/- 4 bursts/min; Delta233 +/- 90 arbitrary units/min from normothermic baseline), which was not significantly different from the algebraic sum of HDR during normothermia and whole body heating (Delta15 +/- 4 bursts/min; Delta205 +/- 55 arbitrary units/min). These data suggest that heat stress does not modify the vestibulosympathetic reflex and that both the vestibulosympathetic and thermal reflexes are robust, independent sympathetic nervous system activators.     

Prolonged muscle vibration increases stretch reflex amplitude, motor unit discharge rate, and force fluctuations in a hand muscle.

The purpose of this study was to compare the influence of prolonged vibration of a hand muscle on the amplitude of the stretch reflex, motor unit discharge rate, and force fluctuations during steady, submaximal contractions. Thirty-two young adults performed 10 isometric contractions at a constant force (5.0 +/- 2.3% of maximal force) with the first dorsal interosseus muscle. Each contraction was held steady for 10 s, and then stretch reflexes were evoked. Subsequently, 20 subjects had vibration applied to the relaxed muscle for 30 min, and 12 subjects received no vibration. The muscle vibration induced a tonic vibration reflex. The intervention (vibration or no vibration) was followed by 2 sets of 10 constant-force contractions with applied stretches (After and Recovery trials). The mean electromyogram amplitude of the short-latency component of the stretch reflex increased by 33% during the After trials (P < 0.01) and by 38% during the Recovery trials (P < 0.01). The standard deviation of force during the steady contractions increased by 21% during the After trials (P < 0.05) and by 28% during the Recovery trials (P < 0.01). The discharge rate of motor units increased from 10.3 +/- 2.7 pulses/s (pps) before vibration to 12.2 +/- 3.1 pps (P < 0.01) during the After trials and to 11.9 +/- 2.6 pps during the Recovery trials (P < 0.01). There was no change in force fluctuations or stretch reflex magnitude for the subjects in the Control group. The results indicate that prolonged vibration increased the short-latency component of the stretch reflex, the discharge rate of motor units, and the fluctuations in force during contractions by a hand muscle. These adjustments were necessary to achieve the target force due to the vibration-induced decrease in the force capacity of the muscle.     

Baroreflex control of the rat tail circulation in normothermia and hyperthermia

The role of thermoregulatory background in the baroreceptor reflex control of the tail circulation was investigated 1) in anesthetized rats with a constant flow technique and 2) in conscious rats by measuring tail blood flow (venous occlusion plethysmography). In series I, during normothermia, systemic intravenous phenylephrine infusion increased mean arterial pressure (MAP) by 61.0 +/- 3.6 mmHg and induced a reflex decrease in tail perfusion pressure (TPP) from 105.0 +/- 6.3 to 84.2 +/- 4.4 mmHg (P less than 0.005). Hyperthermia decreased TPP to 66.5 +/- 5.1 mmHg (P less than 0.001) and abolished the TPP response to increased MAP (P greater than 0.05). Increases in MAP via systemic infusion of whole blood caused reductions in TPP during normothermia but failed to reduce TPP further during hyperthermia. Graded decreases in MAP during both normothermia and hyperthermia caused tail vasoconstriction. The increase in TPP was greater (P less than 0.025) during hyperthermia. In series II, conscious animals showed similar responses to hemorrhage. Graded decreases in MAP produced graded decreases in tail vascular conductance (TVC, ml.100 ml-1.min-1.100 mmHg-1). The slope of the TVC-MAP relationship averaged 0.011 +/- 0.003 TVC U/mmHg during normothermia and was markedly steeper (P less than 0.01) during hyperthermia (1.99 +/- 0.39 TVC U/mmHg). Thus the participation of the cutaneous vasculature of the rat in baroreceptor reflexes depends on thermal status, probably through the level of background sympathetic vasoconstrictor nerve activity.     

Arterial baroreflex control of muscle sympathetic nerve activity in the transition from rest to steady-state dynamic exercise in humans

We sought to investigate arterial baroreflex (ABR) control of muscle sympathetic nerve activity (MSNA) in the transition from rest to steady-state dynamic exercise. This was accomplished by assessing the relationship between spontaneous variations in diastolic blood pressure (DBP) and MSNA at rest and during the time course of reaching steady-state arm cycling at 50% peak oxygen uptake (VO(2peak)). Specifically, DBP-MSNA relations were examined in eight subjects (25 +/- 1 yr) at the start of unloaded arm cycling and then during the initial and a later period of arm cycling once the 50% VO(2peak) work rate was achieved. Heart rate and arterial blood pressure were progressively increased throughout exercise. Although resting MSNA [16 +/- 2 burst/min; 181 +/- 36 arbitrary units (au) total activity] was unchanged during unloaded cycling, MSNA burst frequency and total activity were significantly elevated during the initial (27 +/- 4 burst/min; 367 +/- 76 au; P < 0.05) and later (36 +/- 7 burst/min; 444 +/- 91 au; P < 0.05) periods of exercise. The relationships between DBP and burst incidence, burst strength, and total MSNA were progressively shifted rightward from unloaded to the initial to the later period of 50% VO(2peak) arm cycling without any changes in the slopes of the linear regressions (i.e., ABR sensitivity). Thus a continuous and dynamic resetting of the ABR control of MSNA occurred during the transition from rest to steady-state dynamic exercise. These findings indicate that the ABR control of MSNA was well maintained throughout dynamic exercise in humans, progressively being reset to operate around the exercise-induced elevations in blood pressure and MSNA without any changes in reflex sensitivity.     

Interstitial pH, K(+), lactate, and phosphate determined with MSNA during exercise in humans

The purpose of the present study was to use the microdialysis technique to simultaneously measure the interstitial concentrations of several putative stimulators of the exercise pressor reflex during 5 min of intermittent static quadriceps exercise in humans (n = 7). Exercise resulted in approximately a threefold (P < 0.05) increase in muscle sympathetic nerve activity (MSNA) and 13 +/- 3 beats/min (P < 0.05) and 20 +/- 2 mmHg (P < 0.05) increases in heart rate and blood pressure, respectively. During recovery, all reflex responses quickly returned to baseline. Interstitial lactate levels were increased (P < 0.05) from rest (1.1 +/- 0.1 mM) to exercise (1. 6 +/- 0.2 mM) and were further increased (P < 0.05) during recovery (2.0 +/- 0.2 mM). Dialysate phosphate concentrations were 0.55 +/- 0. 04, 0.71 +/- 0.05, and 0.48 +/- 0.03 mM during rest, exercise, and recovery, respectively, and were significantly elevated during exercise. At the onset of exercise, dialysate K(+) levels rose rapidly above resting values (4.2 +/- 0.1 meq/l) and continued to increase during the exercise bout. After 5 min of contractions, dialysate K(+) levels had peaked with an increase (P < 0.05) of 0.6 +/- 0.1 meq/l and subsequently decreased during recovery, not being different from rest after 3 min. In contrast, H(+) concentrations rapidly decreased (P < 0.05) from resting levels (69.4 +/- 3.7 nM) during quadriceps exercise and continued to decrease with a mean decline (P < 0.05) of 16.7 +/- 3.8 nM being achieved after 5 min. During recovery, H(+) concentrations rapidly increased and were not significantly different from baseline after 1 min. This study represents the first time that skeletal muscle interstitial pH, K(+), lactate, and phosphate have been measured in conjunction with MSNA, heart rate, and blood pressure during intermittent static quadriceps exercise in humans. These data suggest that interstitial K(+) and phosphate, but not lactate and H(+), may contribute to the stimulation of the exercise pressor reflex.     

Interactive effect of hypoxia and otolith organ engagement on cardiovascular regulation in humans.

We determined the interaction between the vestibulosympathetic reflex and the arterial chemoreflex in 12 healthy subjects. Subjects performed three trials in which continuous recordings of muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP), heart rate (HR), and arterial oxygen saturation were obtained. First, in prone subjects the otolith organs were engaged by use of head-down rotation (HDR). Second, the arterial chemoreflex was activated by inspiration of hypoxic gas (10% O2 and 90% N2) for 7 min with HDR being performed during minute 6. Third, hypoxia was repeated (15 min) with HDR being performed during minute 14. HDR [means +/- SE; increase (Delta)7 +/- 1 bursts/min and Delta50 +/- 11% for burst frequency and total MSNA, respectively; P < 0.05] and hypoxia (Delta6 +/- 2 bursts/min and Delta62 +/- 29%; P < 0.05) increased MSNA. Additionally, MSNA increased when HDR was performed during hypoxia (Delta11 +/- 2 bursts/min and Delta127 +/- 57% change from normoxia; P < 0.05). These increases in MSNA were similar to the algebraic sum of the individual increase in MSNA elicited by HDR and hypoxia (Delta13 +/- 1 bursts/min and Delta115 +/- 36%). Increases in MAP (Delta3 +/- 1 mmHg) and HR (Delta19 +/- 1 beats/min) during combined HDR and hypoxia generally were smaller (P < 0.05) than the algebraic sum of the individual responses (Delta5 +/- 1 mmHg and Delta24 +/- 2 beats/min for MAP and HR, respectively; P < 0.05). These findings indicate an additive interaction between the vestibulosympathetic reflex and arterial chemoreflex for MSNA. Therefore, it appears that MSNA outputs between the vestibulosympathetic reflex and arterial chemoreflex are independent of one another in humans.     

Effect of systemic B-type natriuretic peptide on cardiac vagal motoneuron activity

Intravenous B-type natriuretic peptide (BNP) enhances the bradycardia of reflexes from the heart, including the von Bezold-Jarisch reflex, but its site of action is unknown. The peptide is unlikely to penetrate the blood-brain barrier but could act on afferent or efferent reflex pathways. To investigate the latter, two types of experiment were performed on urethane-anesthetized (1.4 g/kg iv) rats. First, the activity was recorded extracellularly from single cardiac vagal motoneurons (CVMs) in the nucleus ambiguus. CVMs were identified by antidromic activation from the cardiac vagal branch and by their barosensitivity. Phenyl biguanide (PBG), injected via the right atrium in bolus doses of 1-5 mug to evoke the von Bezold-Jarisch reflex, caused a dose-related increase in CVM activity and bradycardia. BNP infusion (25 pmol.kg(-1).min(-1) iv) significantly enhanced both the CVM response to PBG (n = 5 rats) and the reflex bradycardia, but the log-linear relation between those two responses over a range of PBG doses was unchanged by BNP. The reflex bradycardia was not enhanced in five matched time-control rats receiving only vehicle infusions. In five other rats the cervical vagi were cut and the peripheral right vagus was stimulated supramaximally at frequencies of 1-20 Hz. The bradycardic responses to these stimuli were unchanged before, during, and after BNP infusion. We conclude that systemic BNP in a moderate dose enhances the von Bezold-Jarisch reflex activation of CVM, in parallel with the enhanced reflex bradycardia. That enhancement is due entirely to an action before the vagal efferent arm of the reflex pathway.     

Effect of hypoxia on the excitability of two cranial reflexes in unanaesthetized fetal sheep

In fetal sheep acute hypoxia causes a decreased incidence of breathing movements and motor activity, and the excitability of polysynaptic reflexes in the hindlimbs is depressed. To determine whether this inhibitory effect extends to other areas in the fetal CNS, we have studied the effect of hypoxia on two reflexes with cranial pathways. The digastric (jaw opening) reflex was elicited by stimulation of the dental nerve through a pair of stainless steel electrodes implanted into the mandible (4 fetuses). The thyroarytenoid muscle of the larynx was reflexly activated by stimulation of the superior laryngeal nerve by a cuff electrode (4 fetuses). Low level stimulation at 1.5-2 X threshold was repeated at approximately 2 min intervals for 3-4 h; the stimulation did not alter the pattern of electrocortical activity, breathing movements, or cause arousal. The amplitude of the digastric reflex was greatest during low voltage electrocortical activity; conversely, the amplitude of the thyroarytenoid reflex was greatest during high voltage electrocortical activity. Isocapnic hypoxia lasting 30-60 min (16 trials), in which the PaO2 was reduced to 12-14 mmHg, did not reduce the amplitude of either reflex. The reduction of thyroarytenoid reflex amplitude which normally occurred during low voltage electrocortical activity was not present during hypoxia. These experiments show that the inhibitory effects of hypoxia on spinal reflexes, breathing movements and motor activity do not include these cranial pathways.     

Plasma levels of cortisol and oxytocin,and uterine activity after cervical artificial insemination in the ewe

The objective was to compare in the ewe the effects of easy and difficult procedures for artificial insemination (AI) (as related to rapid or poor accessibility of the cervix, respectively) on plasma cortisol (CORT) and oxytocin (OT), and uterine motility. All AI were simulated using a catheter empty of semen to study genital and environmental stimuli only. In experiment 1, 40 ewes were sampled after Al, and whether it was an easy or difficult procedure was reported for each animal. While CORT concentrations rose to a similar amount in all ewes, whatever the Al procedure, a significant OT response occurred after a difficult procedure only (n = 18) (17.4 +/- 1.7 versus 12.7 +/- 0.7 pg x mL(-1) before Al, p < 0.05). In experiment 2, uterine activity was monitored in 4 ewes using an implantable telemetric transmitter equipped with an intrauterine pressure catheter. An increased uterine activity occurred during 2 +/- 1 min after an easy Al (n = 5), whereas the evoked activity lasted for 15 +/- 4 min after a difficult Al (p < 0.001, n = 7). A similar long-lasting response occurred after OT administration (100 mIU, i.v.). We concluded that the increase in uterine motility after a difficult Al resulted from a reflex release of OT, and not to a "stress" effect.     

Nociceptin in rVLM mediates electroacupuncture inhibition of cardiovascular reflex excitatory response in rats.

Electroacupuncture (EA) at Neiguan-Jianshi acupoints through an opioid mechanism inhibits the cardiovascular pressor response induced by mechanical stimulation of the stomach. Because nociceptin also may regulate cardiovascular activity through its action in the brain stem, we hypothesized that this neuromodulator serves a role in the EA-related inhibitory effect. Blood pressure in ventilated male Sprague-Dawley rats (400-600 g) anesthetized by ketamine and alpha-chloralose was measured during balloon inflation of the stomach. Gastric distension with 6-8 ml of air induced consistent pressor reflexes of 26 +/- 1 mmHg that could be repeated every 10 min for 100 min. When nociceptin (10 nM) was microinjected into the rostral ventrolateral medulla (rVLM), the pressor response induced by gastric distension was inhibited by 68 +/- 6%. Thirty minutes of EA also decreased the reflex response by 75 +/- 11%; microinjection of saline into the rVLM did not alter the inhibitory effect of EA. In contrast, microinjection of a nociceptin receptor antagonist into the rVLM promptly reversed the EA response. Pretreatment with the opioid receptor antagonist naloxone did not influence the EA-like inhibitory effect of nociceptin on the distension-induced pressor reflex (22 +/- 1 to 8 +/- 2 mmHg). Furthermore, a mu-opioid receptor agonist microinjected into the rVLM after microinjection of a nociceptin receptor antagonist during EA promptly reversed the nociceptin receptor antagonist-related inhibition of the EA effect. Thus, in addition to the classical opioid system, nociceptin, through opioid receptor-like-1 receptor stimulation in the rVLM, participates in the modulatory influence of EA on reflex-induced increases in blood pressure.     

Ghrelin accelerates gastric emptying via early manifestation of antro-pyloric coordination in conscious rats

Ghrelin is known to enhance gastric motility and accelerate gastric emptying of liquid and solid food in rats. As solid gastric emptying is regulated by the coordinated motor pattern between the antrum and pylorus (antro-pyloric coordination), we studied the correlation between solid gastric emptying and antro-pyloric coordination in response to ghrelin. Rats were given 1.5 g of solid food after a 24-h fasting. Immediately after the ingestion, ghrelin (0.4-8.0 microg/kg) or saline was administered by intraperitoneal (i.p.) injection. Ninety minutes after the feeding, rats were euthanized and gastric content was removed to calculate gastric emptying. To evaluate the antro-pyloric coordination, strain gauge transducers were sutured on the antrum and pylorus. The incidence of postprandial antro-pyloric coordination was compared between ghrelin-and saline-injected rats. In saline-injected rats, gastric emptying was 58.3+/-3.7% (n=6). Ghrelin (4.0-8.0 microg/kg), accelerated gastric emptying. Maximum effect was obtained by ghrelin (4.0 microg/kg), which significantly accelerated gastric emptying to 77.4+/-3.7% (n=6, p<0.05). The number of antro-pyloric coordination 20-40 min after feeding was significantly increased in ghrelin-injected rats, compared to that of saline-injected rats (n=4, p<0.05). It is suggested that enhanced antro-pyloric coordination play an important role in accelerated solid gastric emptying induced by ghrelin.     

Vestibulosympathetic reflex during the early follicular and midluteal phases of the menstrual cycle

Evidence suggests that both the arterial baroreflex and vestibulosympathetic reflex contribute to blood pressure regulation, and both autonomic reflexes integrate centrally in the medulla cardiovascular center. A previous report indicated increased sympathetic baroreflex sensitivity during the midluteal (ML) phase of the menstrual cycle compared with the early follicular (EF) phase. On the basis of this finding, we hypothesize an augmented vestibulosympathetic reflex during the ML phase of the menstrual cycle. Muscle sympathetic nerve activity (MSNA), mean arterial pressure (MAP), and heart rate responses to head-down rotation (HDR) were measured in 10 healthy females during the EF and ML phases of the menstrual cycle. Plasma estradiol (Delta72 +/- 13 pg/ml, P < 0.01) and progesterone (Delta8 +/- 2 ng/ml, P < 0.01) were significantly greater during the ML phase compared with the EF phase. The menstrual cycle did not alter resting MSNA, MAP, and heart rate (EF: 13 +/- 3 bursts/min, 80 +/- 2 mmHg, 65 +/- 2 beats/min vs. ML: 14 +/- 3 bursts/min, 81 +/- 3 mmHg, 64 +/- 3 beats/min). During the EF phase, HDR increased MSNA (Delta3 +/- 1 bursts/min, P < 0.02) but did not change MAP or heart rate (Delta0 +/- 1 mmHg and Delta1 +/- 1 beats/min). During the ML phase, HDR increased both MSNA and MAP (Delta4 +/- 1 bursts/min and Delta3 +/- 1 mmHg, P < 0.04) with no change in heart rate (Delta0 +/- 1 beats/min). MSNA and heart rate responses to HDR were not different between the EF and ML phases, but MAP responses to HDR were augmented during the ML phase (P < 0.03). Our results demonstrate that the menstrual cycle does not influence the vestibulosympathetic reflex but appears to alter MAP responses to HDR during the ML phase.     

Hemodynamic effects of long-term converting-enzyme inhibition in renal hypertensive rats

The hemodynamic effects of a converting-enzyme inhibitor (CEI) given during 12 consecutive hours were studied in severe chronic renal hypertensive and normotensive Wistar rats. Hemodynamic parameters were obtained by thermodilution method in conscious unrestrained animals twenty-four hours after surgery. A bolus of CEI induced a significant decrease of mean arterial pressure (MAP) (from 192.2 +/- 8.2 to 163.3 +/- 5.9 mmHg, p less than 0.001) and total peripheral resistance (TPR) (from 7.69 +/- 0.53 to 5.83 +/- 0.33 mmHg.min/ml 100 g) in hypertensive animals. Cardiac index (CI) and heart rate increased significantly (p less than 0.05). Infusion of CEI to hypertensive animals during 12 consecutive hours produced a further progressive decrease in MAP and TPR (p less than 0.05) and an increase in CI (p less than 0.05). Heart rate did not change. Acute and prolonged infusions of CEI to normotensive group induced less but similar effect to those observed in hypertensive group. These results suggest that an increase of the renin-angiotensin system activity is the principal mechanism involved in the maintenance of high blood pressure during chronic phase of renal hypertension on the rats.     

Nitric oxide modulates sympathoexcitatory cardiac-cardiovascular reflexes elicited by bradykinin

A number of studies have demonstrated an important role for nitric oxide (NO) in central and peripheral neural modulation of sympathetic activity. To assess the interaction and integrative effects of NO release and sympathetic reflex actions, we investigated the influence of inhibition of NO on cardiac-cardiovascular reflexes. In anesthetized, sinoaortic-denervated and vagotomized cats, transient reflex increases in arterial blood pressure (BP) were induced by application of bradykinin (BK, 0.1-10 microg/ml) to the epicardial surface of the heart. The nonspecific NO synthase (NOS) inhibitor NG-monomethyl-L-arginine (L-NMMA, 10 mg/kg iv) was then administered and stimulation was repeated. L-NMMA increased baseline mean arterial pressure (MAP) from 129 +/- 8 to 152 +/- 9 mmHg and enhanced the change in MAP in response to BK from 32 +/- 3 to 39 +/- 5 mmHg (n = 9, P < 0.05). Pulse pressure was significantly enhanced during the reflex response from 6 +/- 4 to 27 +/- 6 mmHg after L-NMMA injection due to relatively greater potentiation of the rise in systolic BP. Both the increase in baseline BP and the enhanced pressor reflex were reversed by L-arginine (30 mg/kg iv). Because L-NMMA can inhibit both brain and endothelial NOS, the effects of 7-nitroindazole (7-NI, 25 mg/kg ip), a selective brain NOS inhibitor, on the BK-induced cardiac-cardiovascular pressor reflex also were examined. In contrast to L-NMMA, we observed significant reduction of the pressor response to BK from 37 +/- 5 to 18 +/- 3 mmHg 30 min after the administration of 7-NI (n = 9, P < 0.05), an effect that was reversed by L-arginine (300 mg/kg iv, n = 7). In a vehicle control group for 7-NI (10 ml of peanut oil ip), the pressor response to BK remained unchanged (n = 6, P > 0.05). In conclusion, neuronal NOS facilitates, whereas endothelial NOS modulates, the excitatory cardiovascular reflex elicited by chemical stimulation of sympathetic cardiac afferents.     

Spinal reflexes and coactivation of ankle muscles during a submaximal fatiguing contraction.

This study examined the involvement of spinal mechanisms in the control of coactivation during a sustained contraction of the ankle dorsiflexors at 50% of maximal voluntary contraction. Changes in the surface electromyogram (EMG) of the tibialis anterior and of two antagonist muscles, the soleus and lateral gastrocnemius, were investigated during and after the fatigue task. Concurrently, the compound action potential (M-wave) and the Hoffmann reflex of the soleus and lateral gastrocnemius were recorded. The results showed that the torque of the ankle dorsiflexors and the average EMG of the tibialis anterior during maximal voluntary contraction declined by 40.9 +/- 17.7% (mean +/- SD; P < 0.01) and 37.0 +/- 19.9% (P < 0.01), respectively, at task failure. During the submaximal fatiguing contraction, the average EMG of both the agonist and antagonist muscles increased, leading to a nearly constant ratio at the end of the contraction when normalized to postfatigue values. In contrast to the monotonic increase in average EMG of the antagonist muscles, the excitability of their spinal reflex pathways exhibited a biphasic modulation. The amplitude of the Hoffman reflexes in the soleus and lateral gastrocnemius increased to 147.5 +/- 52.9% (P < 0.05) and 166.7 +/- 74.9% (P < 0.01), respectively, during the first 20% of the contraction and then subsequently declined to 66.3 +/- 44.8 and 74.4 +/- 44.2% of their initial values. In conclusion, the results show that antagonist coactivation did not contribute to task failure. The different changes in voluntary EMG activity and spinal reflex excitability in the antagonist muscles during the fatiguing contraction support the concept that the level of coactivation is controlled by supraspinal rather than spinal mechanisms. The findings indicate, however, that antagonist coactivation cannot simply be mediated by a central descending "common drive" to the motor neuron pools of the agonist-antagonist muscle pairs. Rather, they suggest a more subtle regulation of the drive, possibly through presynaptic mechanisms, to the motoneurons that innervate the antagonist muscles.     

Effect of baroreflex loading on the responsiveness of the vestibulosympathetic reflex in humans.

Activation of the vestibular otolith organs with head-down rotation (HDR) increases muscle sympathetic nerve activity (MSNA) in humans. Previously, we demonstrated this vestibulosympathetic reflex (VSR) elicits increases in MSNA during baroreflex unloading (i.e., lower body negative pressure) in humans. Whether such an effect persists during baroreflex loading is unknown. We tested the hypothesis that the ability of the VSR to increase MSNA is preserved during baroreflex unloading and inhibited during baroreflex loading. Ten subjects (26 +/- 1 yr) performed three trials of HDR to activate the VSR. These trials were performed after a period of sustained saline (control), nitroprusside (baroreflex unloading: 0.8-1.0 microg.kg(-1).min(-1)), and phenylephrine (baroreflex loading: 0.6-0.8 microg.kg(-1).min(-1)) infusion. Nitroprusside infusion decreased (Delta7 +/- 1 mmHg, where Delta is change; P < 0.001) and phenylephrine infusion increased mean arterial pressure (Delta8 +/- 1 mmHg; P < 0.001) at rest. HDR performed during the control [Delta3 +/- 2 bursts/min, Delta314 +/- 154 arbitrary units (au) total activity, Delta41 +/- 18% total activity; P < 0.05] and nitroprusside trials [Delta5 +/- 2 bursts/min, Delta713 +/- 241 au total activity, Delta49 +/- 20% total activity; P < 0.05] increased MSNA similarly despite significantly elevated levels at rest (13 +/- 2 to 26 +/- 3 bursts/min) in the latter. In contrast, HDR performed during the phenylephrine trial failed to increase MSNA (Delta0 +/- 1 bursts/min, Delta-15 +/- 33 au total activity, Delta-8 +/- 21% total activity). These results confirm previous findings that the ability of the VSR to increase MSNA is preserved during baroreflex unloading. In contrast, the ability of the VSR to increase MSNA is abolished during baroreflex loading. These results provide further support for the concept that the VSR may act primarily to defend against hypotension in humans.     

Glutamate release in midbrain periaqueductal gray by activation of skeletal muscle receptors and arterial baroreceptors

We have previously reported that both skeletal muscle receptor and arterial baroreceptor afferent inputs activate neurons in the dorsolateral (DL) and lateral regions of the midbrain periaqueductal gray (PAG). In this study, we determined whether the excitatory amino acid glutamate (Glu) is released to mediate the increased activity in these regions. Static contraction of the triceps surae muscle for 4 min was evoked by electrical stimulation of the L7 and S1 ventral roots in cats. Activation of arterial baroreceptor was induced by intravenous injection of phenylephrine. The endogenous release of Glu from the PAG was recovered with the use of a microdialysis probe. Glu concentration was measured by the HPLC method. Muscle contraction increased mean arterial pressure (MAP) from 98 +/- 10 to 149 +/- 12 mmHg (P < 0.05) and increased Glu release in the DL and lateral regions of the middle PAG from 0.39 +/- 0.10 to 0.73 +/- 0.12 microM (87%, P < 0.05) in intact cats. After sinoaortic denervation and vagotomy were performed, contraction increased MAP from 95 +/- 12 to 158 +/- 15 mmHg, and Glu from 0.34 +/- 0.08 to 0.54 +/- 0.10 microM (59%, P < 0.05). The increases in arterial pressure and Glu were abolished by muscle paralysis. Phenylephrine increased MAP from 100 +/- 13 to 162 +/- 22 mmHg and increased Glu from 0.36 +/- 0.10 to 0.59 +/- 0.18 microM (64%, P < 0.05) in intact animals. Denervation abolished this Glu increase. Summation of the changes in Glu evoked by muscle receptor and arterial baroreceptor afferent inputs was greater than the increase in Glu produced when both reflexes were activated simultaneously in intact state (123% vs. 87%). These data demonstrate that activation of skeletal muscle receptors evokes release of Glu in the DL and lateral regions of the middle PAG, and convergence of afferent inputs from muscle receptors and arterial baroreceptors in these regions inhibits the release of Glu. These results suggest that the PAG is a neural integrating site for the interaction between the exercise pressor reflex and the arterial baroreceptor reflex.