Quantitative analysis of flavanones and chalcones from willow bark.

Willow bark extracts are used for the treatment of fever, pain and inflammation. Recent clinical and pharmacological research revealed that not only the salicylic alcohol derivatives, but also the polyphenols significantly contribute to these effects. Quantitative analysis of the European Pharmacopoeia still focuses on the determination of the salicylic alcohol derivatives. The objective of the present study was the development of an effective quantification method for the determination of as many flavanone and chalcone glycosides as possible in Salix purpurea and other Salix species as well as commercial preparations thereof. As Salix species contain a diverse spectrum of the glycosidated flavanones naringenin, eriodictyol, and the chalcone chalconaringenin, a subsequent acidic and enzymatic hydrolysis was developed to yield naringenin and eriodictyol as aglycones, which were quantified by HPLC. The 5-O-glucosides were cleaved with 11.5% TFA before subsequent hydrolysis of the 7-O-glucosides with an almond ß-glucosidase at pH 6-7. The method was validated with regard to LOD, LOQ, intraday and interday precision, accuracy, stability, recovery, time of hydrolysis, robustness and applicability to extracts. All 5-O- and 7-O-glucosides of naringenin, eriodictyol and chalconaringenin were completely hydrolysed and converted to naringenin and eriodictyol. The LOD of the HPLC method was 0.77 µM of naringenin and 0.45 µM of eriodictyol. The LOQ was 2.34 µM of naringenin and 1.35 µM for eriodictyol. The method is robust with regard to sample weight, but susceptible concerning enzyme deterioration. The developed method is applicable to the determination of flavanone and chalcone glycosides in willow bark and corresponding preparations.

Low cell pH depresses peak power in rat skeletal muscle fibres at both 30 degrees C and 15 degrees C: implications for muscle fatigue.

Historically, an increase in intracellular H(+) (decrease in cell pH) was thought to contribute to muscle fatigue by direct inhibition of the cross-bridge leading to a reduction in velocity and force. More recently, due to the observation that the effects were less at temperatures closer to those observed in vivo, the importance of H(+) as a fatigue agent has been questioned. The purpose of this work was to re-evaluate the role of H(+) in muscle fatigue by studying the effect of low pH (6.2) on force, velocity and peak power in rat fast- and slow-twitch muscle fibres at 15 degrees C and 30 degrees C. Skinned fast type IIa and slow type I fibres were prepared from the gastrocnemius and soleus, respectively, mounted between a force transducer and position motor, and studied at 15 degrees C and 30 degrees C and pH 7.0 and 6.2, and fibre force (P(0)), unloaded shortening velocity (V(0)), force-velocity, and force-power relationships determined. Consistent with previous observations, low pH depressed the P(0) of both fast and slow fibres, less at 30 degrees C (4-12%) than at 15 degrees C (30%). However, the low pH-induced depressions in slow type I fibre V(0) and peak power were both significantly greater at 30 degrees C (25% versus 9% for V(0) and 34% versus 17% for peak power). For the fast type IIa fibre type, the inhibitory effect of low pH on V(0) was unaltered by temperature, while for peak power the inhibition was reduced at 30 degrees C (37% versus 18%). The curvature of the force-velocity relationship was temperature sensitive, and showed a higher a/P(0) ratio (less curvature) at 30 degrees C. Importantly, at 30 degrees C low pH significantly depressed the ratio of the slow type I fibre, leading to less force and velocity at peak power. These data demonstrate that the direct effect of low pH on peak power in both slow- and fast-twitch fibres at near-in vivo temperatures (30 degrees C) is greater than would be predicted based on changes in P(0), and that the fatigue-inducing effects of low pH on cross-bridge function are still substantial and important at temperatures approaching those observed in vivo.

Influence of hypercapnia and hypocapnia on bladder contractions and their respiratory consequences.

Rhythmic contractions of the detrusor muscle, induced by gradual filling of the urinary bladder in decerebrate or anesthetized cats, are accompanied by decreased inspiratory activity in motor nerves to respiratory muscles, particularly those of the upper airway. We have examined the influence of hypercapnia and hypocapnia on these contractions and the accompanying activities of the phrenic and hypoglossal nerves in decerebrate, vagotomized, paralyzed and ventilated cats, some of which had denervated carotid chemoreceptors. Hypercapnia slowed, and then reversibly abolished bladder contractions in most animals, regardless of the state of the carotid chemoreceptors. Bladder contractions were well maintained in progressive hypocapnia, even at end-tidal CO(2) levels below the 'apneic' thresholds of the hypoglossal and phrenic activities. The reductions of the nerve activities in response to bladder contractions were not significantly altered by hypercapnia or hypocapnia. The abolition of bladder contractions by hypercapnia is unlikely to reflect a direct effect of CO(2) or H+ ion on the contractile mechanism of the detrusor muscle, but may be based on inhibition of stretch receptors in the bladder wall and/or an effect of CO(2) or H+ in or near the micturition centers in the brain stem.

Respiratory response to mechanical stimulation of the gallbladder.

Since stimuli from abdominal or pelvic viscera can affect respiratory muscle function, we hypothesized that mechanical stimulation of the gallbladder would result in inhibition of motor activity to the diaphragm and to upper airway muscles. We studied 12 decerebrate, vagotomized, paralyzed, artificially ventilated cats and recorded hypoglossal (HG) and phrenic (PHR) nerve activities while applying 600-1000 g of traction on the gallbladder during four respiratory cycles. Traction resulted in an initial reduction of PHR activity to 87.6+/-15.0% (mean+/-S.D.% of its baseline value), a reduction of HG activity to 74.2+/-27.5% and a lengthening of expiratory time to 178.8+/-81.0%. Subsequently, PHR activity and expiratory time returned toward control values, while HG remained diminished, at 66.4+/-19.1%. Our results show that mechanical stimulation of the gallbladder results in a respiratory inhibition with a disproportionate reduction in HG activity relative to PHR discharge. We speculate that gallbladder stimulation by contractions or surgery may compromise breathing by inhibition of phrenic discharge and upper airway obstruction.

Functional properties of slow and fast gastrocnemius muscle fibers after a 17-day spaceflight.

The purpose of this investigation was to study the effects of a 17-day spaceflight on the contractile properties of individual fast- and slow-twitch fibers isolated from biopsies of the fast-twitch gastrocnemius muscle of four male astronauts. Single chemically skinned fibers were studied during maximal Ca2+-activated contractions with fiber myosin heavy chain (MHC) isoform expression subsequently determined by SDS gel electrophoresis. Spaceflight had no significant effect on the mean diameter or specific force of single fibers expressing type I, IIa, or IIa/IIx MHC, although a small reduction in average absolute force (P(o)) was observed for the type I fibers (0.68 +/- 0.02 vs. 0.64 +/- 0.02 mN, P < 0.05). Subject-by-flight interactions indicated significant intersubject variation in response to the flight, as postflight fiber diameter and P(o) where significantly reduced for the type I and IIa fibers obtained from one astronaut and for the type IIa fibers from another astronaut. Average unloaded shortening velocity [V(o), in fiber lengths (FL)/s] was greater after the flight for both type I (0.60 +/- 0.03 vs. 0.76 +/- 0.02 FL/s) and IIa fibers (2.33 +/- 0.25 vs. 3.10 +/- 0.16 FL/s). Postflight peak power of the type I and IIa fibers was significantly reduced only for the astronaut experiencing the greatest fiber atrophy and loss of P(o). These results demonstrate that 1) slow and fast gastrocnemius fibers show little atrophy and loss of P(o) but increased V(o) after a typical 17-day spaceflight, 2) there is, however, considerable intersubject variation in these responses, possibly due to intersubject differences in in-flight physical activity, and 3) in these four astronauts, fiber atrophy and reductions in P(o) were less for slow and fast fibers obtained from the phasic fast-twitch gastrocnemius muscle compared with slow and fast fibers obtained from the slow antigravity soleus [J. J. Widrick, S. K. Knuth, K. M. Norenberg, J. G. Romatowski, J. L. W. Bain, D. A. Riley, M. Karhanek, S. W. Trappe, T. A. Trappe, D. L. Costill, and R. H. Fitts. J Physiol (Lond) 516: 915-930, 1999].

Respiratory response to baroreceptor stimulation and spontaneous contractions of the urinary bladder.

Spontaneous contractions of the urinary bladder (SBCs) and experimental elevations of carotid sinus pressure (CSP) have been shown to result in respiratory inhibition with preferential reduction in hypoglossal (HG) nerve activity as compared with that of phrenic nerve discharge. We assessed the interaction between these respiratory inhibitory stimuli in decerebrate, vagotomized, paralyzed and artificially ventilated cats. We denervated the right carotid sinus and pressurized the isolated left carotid sinus region within the linear range of the baroreflex, while maintaining systemic arterial pressure at approximately 100 mmHg. We monitored the HG and phrenic nerve responses to SBCs, to elevations in CSP between SBCs, and to elevations in CSP during SBCs. Our results show that superimposing these stimuli results in respiratory inhibition, especially of HG activity, that exceeds that resultant from either stimulus alone. We speculate that the combined presence of SBCs and episodic hypertension may contribute to the development of periodic breathing or obstructive apnea, particularly during sleep.

Respiratory response to spontaneous contractions of the urinary bladder in awake and decerebrate rats.

Spontaneous contractions of the urinary bladder (SBCs) have been shown to decrease the frequency and depth of respiration in anesthetized or unanesthetized, decerebrate cats. The respiratory responses to bladder voiding reflexes in the awake state have not been previously addressed. Because a chronic rat model for the study of bladder function has been established and breathing measurements can be made in the awake rat, we chose the rat as an experimental model to assess whether SBCs would alter breathing in the conscious, intact animal. Respiratory frequency increased during bladder contractions but tidal volume remained unaffected. To assess whether the respiratory response to bladder reflexes in rats differed from that previously observed in cats, we also studied decerebrate, vagotomized, paralyzed and artificially ventilated rats. Contrary to the respiratory inhibition observed in decerebrate cats, phrenic and hypoglossal nerve activities remained unaffected during SBCs in decerebrate rats. These results indicate a species difference in the coupling between respiration and bladder voiding reflexes.

Bladder contractions alter inspiratory termination by superior laryngeal and intercostal nerve stimulation.

Gradual distension of the urinary bladder evokes spontaneous bladder contractions (SBCs), which are associated with reduced inspiratory activity in the phrenic and other inspiratory motor nerves. We examined the influence of isovolumetric SBCs on the threshold for termination of phrenic inspiration by electrical stimulation of superior laryngeal and/or mid-thoracic intercostal nerves (ICN) in decerebrate, vagotomized, paralyzed, ventilated cats. Although SBCs reduced phrenic inspiratory activity, the threshold for inspiratory termination by nerve stimulation was increased. The results emphasize the complexity of the synaptic connections among brain stem neurons governing micturition and breathing.

Effects of experimental cortical seizures on respiratory motor nerve activities in piglets.

Airway obstruction at the level of the larynx causes respiratory insufficiency during experimental seizures in spontaneously breathing, anesthetized piglets (T. E. Terndrup and W. E. Fordyce, Pediatr. Res., 38: 61-66, 1995). To investigate further the neural mechanisms of this obstruction, the activities of the phrenic nerve (PH) and the recurrent laryngeal motor branches to the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles were analyzed in 11 anesthetized, vagotomized, paralyzed, and ventilated piglets. After a control recording period, seizures were induced by subcortical penicillin G injections. Compared with baseline conditions, nerve activities became irregular during seizures. Extraneous TA bursts during PH activation were evident in all piglets during seizures. During ictal phases of seizures, the peak integrated activities of the PH and the expiratory component of the PCA, but not TA or inspiratory PCA activities, were significantly decreased compared with interictal phases. During seizures, a significant delay in the onset of the inspiratory component of PCA activation with respect to the onset of the PH was observed. This study helps to explain respiratory impairment during cortical seizures by providing evidence of impaired timing of activation of laryngeal dilator mechanisms and coordination with those activating the diaphragm. Cyclical PH inhibition during high-intensity cortical discharges may provide a secondary mechanism producing respiratory insufficiency during seizures.

Effect of a 17 day spaceflight on contractile properties of human soleus muscle fibres.

1. Soleus biopsies were obtained from four male astronauts 45 days before and within 2 h after a 17 day spaceflight. 2. For all astronauts, single chemically skinned post-flight fibres expressing only type I myosin heavy chain (MHC) developed less average peak Ca2+ activated force (Po) during fixed-end contractions (0.78 +/- 0. 02 vs. 0.99 +/- 0.03 mN) and shortened at a greater mean velocity during unloaded contractions (Vo) (0.83 +/- 0.02 vs. 0.64 +/- 0.02 fibre lengths s-1) than pre-flight type I fibres. 3. The flight-induced decline in absolute Po was attributed to reductions in fibre diameter and/or Po per fibre cross-sectional area. Fibres from the astronaut who experienced the greatest relative loss of peak force also displayed a reduction in Ca2+ sensitivity. 4. The elevated Vo of the post-flight slow type I fibres could not be explained by alterations in myosin heavy or light chain composition. One alternative possibility is that the elevated Vo resulted from an increased myofilament lattice spacing. This hypothesis was supported by electron micrographic analysis demonstrating a reduction in thin filament density post-flight. 5. Post-flight fibres shortened at 30 % higher velocities than pre-flight fibres at external loads associated with peak power output. This increase in shortening velocity either reduced (2 astronauts) or prevented (2 astronauts) a post-flight loss in fibre absolute peak power (microN (fibre length) s-1). 6. The changes in soleus fibre diameter and function following spaceflight were similar to those observed after 17 days of bed rest. Although in-flight exercise countermeasures probably reduced the effects of microgravity, the results support the idea that ground-based bed rest can serve as a model of human spaceflight. 7. In conclusion, 17 days of spaceflight decreased force and increased shortening velocity of single Ca2+-activated muscle cells expressing type I MHC. The increase in shortening velocity greatly reduced the impact that impaired force production had on absolute peak power.

The effect of exercise and restraint on pectoral muscle metabolism in pigeons.

The effect of various activity regimes on metabolism of pigeon pectoralis was examined by measurement of blood lactate following exercise, total lactate dehydrogenase activity of pectoral muscle, and proportions of specific isoenzymes of pectoral muscle lactate dehydrogenase. Sprint-trained birds had the highest pectoral muscle lactate dehydrogenase activity (1409 IU.g-1 wet tissue), while endurance-trained birds had the highest peak lactate levels (287 mg.dl-1, extra-polated from decay curves) and fastest half-time of the lactate response (4.8 min) following exercise, but the lowest lactate dehydrogenase activity (115 IU.g-1 wet tissue). Immobilization of one wing for 3 weeks following endurance training produced a marked increase in lactate dehydrogenase activity of the immobilized muscle, compared to that in the contralateral pectoralis and endurance-trained muscle. Aerobic forms of the lactate dehydrogenase enzyme (that favor conversion of lactate to pyruvate) predominated in pectoral muscle of endurance-trained birds, while cage-confined birds exhibited primarily the anaerobic isoenzymes. These results demonstrate that conversion of pectoral muscle lactate dehydrogenase isoenzymes, total lactate dehydrogenase activity, and half-time of lactate response after exercise is dependent on activity regime in pigeons. In this respect, pigeon pectoral muscle responds to training and disuse in a manner similar to that of mammalian skeletal muscle.

Influence of lung volume on respiratory responses to spontaneous bladder contractions.

Spontaneous bladder contractions (SBCs) in decerebrate, vagotomized, paralyzed, ventilated cats have been shown to decrease phrenic and hypoglossal inspiratory nerve activities, as well as the activities of other respiratory motor nerves. To determine whether vagal afferents from the lung influence the respiratory inhibition associated with SBCs, we recorded phrenic and hypoglossal nerve activities in decerebrate, paralyzed, vagally intact cats. The animals were ventilated by a servo-respirator, which inflated the lungs in accordance with integrated phrenic nerve activity. Maintained increases in end-expiratory lung volume were produced by the application of 2-10 cm H2O positive end-expiratory pressure (PEEP). SBCs were accompanied by decreases in both phrenic and hypoglossal peak integrated nerve activities, as well as by marked decreases in respiratory frequency. The reduction of respiratory frequency was greater with higher levels of PEEP, a few animals becoming apneic during SBCs. After bilateral vagotomy, SBCs continued to decrease phrenic and hypoglossal peak integrated nerve activities as previously reported, but the reduction of respiratory frequency was much less striking than when the vagi were intact. These results indicate that activity of vagal afferents from the lung augments the respiratory influence of SBCs. Furthermore, SBCs in vagally intact animals can induce periodic breathing.

Roles of the pontine pneumotaxic and micturition centers in respiratory inhibition during bladder contractions.

In decerebrate or anesthetized cats with moderately distended urinary bladders, spontaneous bladder contractions (SBCs) have been shown to decrease phrenic and hypoglossal nerve activities. To determine the involvement of both the pontine micturition center (PMC) and the pneumotaxic center in the respiratory response to SBCs, we recorded phrenic and hypoglossal nerve activities in decerebrate, paralyzed, vagotomized, artificially ventilated cats. Electrical stimulation of the PMC in cats with subthreshold bladder volumes below the threshold for SBCs elicited both increases in intravesical pressure (IVP) and attenuation of respiratory motor nerve activities. Respiration was not altered after PMC lesions, which abolished SBCs, contractions in response to PMC stimulation, and respiratory inhibition due to passive bladder distension. Electrical stimulation of the pneumotaxic center altered respiratory motor nerve activities and increased IVP in cats with subthreshold bladder volumes. Pneumotaxic center lesions caused apneusis, but did not abolish the SBCs, which continued to attenuate the apneustic respiratory motor nerve activity. These results indicate that the PMC is an important component of the reflex pathway from urinary bladder distension to respiratory inhibition, whereas the pneumotaxic center does not appear to be an essential part of this pathway.

Laryngeal CO2 receptors: influence of systemic PCO2 and carbonic anhydrase inhibition.

Responses of laryngeal receptors selected for their responsiveness to 10% intralaryngeal CO2 were recorded in single fibers of the superior laryngeal nerve at a wide range of systemic PCO2 values and before and after carbonic anhydrase inhibition in anesthetized, paralyzed, ventilated cats. Carbonic anhydrase was inhibited, locally, by perfusing the upper airways with either acetazolamide or methazolamide (10(-2) M) or systemically, by injecting acetazolamide intravenously (5, 10, or 25 mg/kg). Of the 58 receptors studied, 55 decreased their discharge rate in response to 10% intralaryngeal CO2, whereas 3 increased their discharge in response to intralaryngeal CO2. The majority of these receptors also increased their discharge rate in response to positive laryngeal pressure. Neither increased nor decreased systemic PCO2 influenced the receptors' baseline discharge rate or their response to intralaryngeal CO2. Topical inhibition of carbonic anhydrase did not consistently alter the maximal inhibitory response to CO2 or the initial rate of change of receptor activity. On the other hand, intravenous injections of acetazolamide caused, within 30 sec, a consistent attenuation of both the initial rate of change and the maximal inhibitory response to intralaryngeal CO2. These results indicate that the sub-set of laryngeal receptors that are sensitive to intralaryngeal CO2 are not responsive to changes in systemic PCO2. The carbonic anhydrase inhibition experiments show that this enzyme plays an important role in the ability of these receptors to detect both transient and steady-state changes in intralaryngeal CO2.

Respiratory motor nerve activities during experimental seizures in cats.

We evaluated respiratory motor nerve activities during experimental seizures induced with subcortical penicillin. The activities of the phrenic (PH), nasolabial (NL), and hypoglossal (HG) nerves and the recurrent laryngeal motor branches to the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles were analyzed in 13 anesthetized, vagotomized, paralyzed, and ventilated cats. During ictal and interictal phases of seizures, nerve activities became irregular and peak integrated nerve activities increased, particularly in the case of the PH nerve. The ictal phase of seizures was associated with increased tonic activity and decreased phasic respiratory discharges, particularly in the cases of the HG, NL, and PCA nerves. During some prolonged ictal discharges, entrainment of nerve activities by cortical spiking was associated with irregular uncoordinated activation, particularly in the TA nerve. These studies help explain respiratory impairment during seizures by providing evidence of impaired coordination between activation of muscles that regulate upper airway patency and activation of the diaphragm.

Effects of castration on antler growth in fallow deer (Dama dama L.).

Morphology and histological structure of antlers grown after castration (performed on March 25) were studied in six young fallow bucks. In the year after castration, antlerogenesis occurred during the species-specific time span, and the shape of the antlers, which remained permanently in velvet, was normal. During a cold period in December/January, the distal parts of the antlers suffered from frostbite and were subsequently detached. The process of sequestration was similar to that leading to normal antler casting. The sequestration sites were soon covered with skin, but (limited) regrowth of antler tissue from the stumps was not observed before late April/early May, i.e., the time of normal antler regeneration. Simultaneously, growth of knobby protuberances started on the surface of the antlers. Histological analysis of biopsies taken on December 20 in the year after castration revealed that the central parts of the antlers consisted of cancellous lamellar bone with mainly secondary osteons. Peripheral to this, the bone tissue (forming the protuberances) was of a more immature nature and exhibited larger intertrabecular spaces. The outermost layer consisted of woven bone formed by intramembranous ossification from the periosteum and was undergoing active growth and remodeling at the time of biopsy. Thus, bone formation at these sites occurred during a period when no antler growth is observed in normal fallow bucks. The velvet covering the bony protuberances was of normal appearance.

Respiratory motor nerve activities during spontaneous bladder contractions.

We monitored spontaneous bladder contractions (SBCs) in decerebrate vagotomized paralyzed ventilated cats while recording respiratory motor nerve activities and intravesical pressure under isovolumetric conditions. Phrenic nerve discharge diminished during SBCs, as did the activities of the hypoglossal nerve, the nasolabial branch of the facial nerve, and inspiratory (posterior cricoarytenoid) and expiratory (thyroarytenoid) branches of the recurrent laryngeal nerve. Hypoglossal activity was most strikingly reduced during SBCs, disappearing completely in some animals. The triangularis sterni nerve exhibited an initial decrease, followed by an increase in activity during SBCs, whereas the cranial iliohypogastric nerve showed increased activity. The changes in nerve activities during SBCs could also be elicited by passive distension of the bladder and were abolished by bilateral section of the pelvic nerves. These findings extend the understanding of reflexes originating from the urinary bladder to include a coordinated respiratory response and suggest that these reflexes may compromise upper airway patency under some conditions.

Influence of hypoxia on ventilatory responses to intralaryngeal CO2 in cats.

In decerebrate, vagotomized cats, introduction of CO2 into the isolated laryngeal airway while systemic PCO2 is held constant evokes dose-related reflex changes in ventilatory activity. Because systemic hypoxia is known to exaggerate ventilatory responses to other types of laryngeal chemostimulation in neonates, we have compared the responses of phrenic and hypoglossal nerve activities to ventilation of the larynx with 10% CO2 during systemic hyperoxia (FIO2 = 1.00) to those during hypoxia (FIO2 = 0.12). Compared with the hyperoxic baseline condition, hypoxia stimulated phrenic activity but attenuated the reduction in phrenic activity evoked by intralaryngeal CO2. Hypoglossal activity was increased by intralaryngeal CO2 and this response appeared to be reduced by hypoxia, but neither of these findings was statistically significant. The response of phrenic activity to intralaryngeal CO2 during systemic hypercapnia was similar to that during hypoxia. The increase of phrenic activity in response to hypoxia was prevented by carotid body resection. Similarly, the hypoxic attenuation of the phrenic response to intralaryngeal CO2 appeared to be absent after carotid body resection, although this finding was not established statistically. These results differ from previous reports of exaggerated laryngeal chemoreflex responses during hypoxia. The difference may reflect differences in the receptors and synaptic mechanisms of the reflexes, the severity and time course of hypoxia or the presence or depth of general anesthesia or sleep.

Hypoglossal and phrenic nerve responses to carotid baroreceptor stimulation.

We examined the relationship between hypoglossal and phrenic nerve activities and carotid sinus pressure. In 12 adult cats that were decerebrate, vagotomized, paralyzed, and mechanically ventilated, we isolated the left carotid sinus for perfusion and denervated the right carotid sinus. Mean arterial blood pressure was maintained at 90-100 mmHg using a low resistance-reservoir containing saline and connected to the abdominal aorta. Constant pressure was applied to the carotid sinus region. We found that increased carotid sinus pressure immediately inhibited inspiratory-synchronous (phasic) hypoglossal nerve activity and that there was a direct inverse relationship between phasic hypoglossal activity and carotid sinus pressure up to a carotid pressure of 285 mmHg. Increased carotid sinus pressure had no effect on tonic hypoglossal nerve activity and only slightly inhibited phrenic nerve activity. Cutting the left carotid sinus nerve abolished this response. We also applied pressure pulses to the carotid sinus at discrete times during the phrenic cycle. We found that baroreceptor inhibition of phasic hypoglossal nerve activity was gated during the phrenic cycle: maximum inhibition occurred when the pulse was applied in late expiration. We conclude that carotid baroreceptor stimulation preferentially inhibits inspiratory synchronous hypoglossal nerve activity and that this afferent information traveling in the carotid sinus nerve is gated by the respiratory control center.