Effects of puImonary stretch receptor afferent stimulation on sympathetic preganglionic neuron firing

URS GERBER AND ~ A W I O POI~OSA Department o f Plry.~io!ogy, ,%dcC;il4 Univc)rsiry, Montreal, P.Q. , Canridn %iG 4Y6

Received September 9, 1977

GI:.RUER. U.. and P o r o s ~ , C. 1978. Effects s f pulmonary stretch receptor afferent stimulation on sympathetic preganglionic neuron firing. Can. %. Phpsiol. Pharmacol. 56, 191-198.

The response of 47 sympathetic preganglionic neurons (SPNs) of the cervical nerve to activation of pulmonary stretch receptors has been studied in Nembaltal-anaesthetixed. paralyzed, thoracotomized, artificially ventilated cats. The discharge of 6276 of the SPNs was depressed by lung inflation or by electrical stimulation of the lowest threshold afferent fibers in the vag~is nerve. The SPNs which were most sensitive to these manoeuvers were those whose discharge had an inspiration-synchronous component. All the SPNs of this type tested were depressed. Their response paralleled that of phrenic motoneurons. The SPNs which were least sensitive to these manoeuvers were those whose firing pattern showed no respiratory modulation. Only 12% of the SPNs of this type tested were depressed. In some SPNs. selective suppression of inspiration-synchronous activity by hypocapnia revealcd a residual firing which could not be altered by pulmonary stretch recep- tor afferent activation. For comparison, the reflex response of the same satnple of SPNs to the systemic arterial pressure increase caused by intravenoa~s injection of nsradrcnaline (5 pg;kg) was studied. The discharge of 85% of the SPNs was depressccl during the pressor eflect of noradrenaline. The frequency of occurrence of depressant effects was similar in respiratory-modulated and nonmodulated SPNs. Also depressed was the residual discharge in hypocapnia of respiratory-nmodulated SPNs. Thus, the distribution in the SPN pool of the depression evoked by a systemic arterial pressure rise contrasts with that caused by activation of pulmonary stretch receptor afferents. These results provide a direct demonstration of the depressant action of puln~onary stretch receptor afferents on SPNs, an action that had previously been hypothesized on the basis of indirect evidence. ?'he observation that activation of these afferents depresses mainly the inspiration-synchronous component of SPN firing suggests that the efiect is predominantly relayed to the SPN pool via the respiratory center.

GEKRER, U., et P o r . o s ~ , C. 1978. Effects of pulmonary stretch receptor a8'erent stimulation on sympathetic preganglionic neuron firing. Can. J. Physiol. Pharmacol. 56, 191-198.

On a i tudi i la rkponse de 47 neilrones prCganglionnaires sympathiques (SPNs) du nerf cervical suite i B'activation de rkcepteurs pulnmonaircs sensibles h 19itiren-aent chez des chats anesthisiks au Nembutal, paralysis. thoracotomisis et ventilks artificiellement. Soixante-deux pour-cent des SPNs montrent une dicharge qui est diminuie par le gonflemcnt des poumons 011 par la stimulation klectrique A un seuil minimum des fibres affirentes du nerf vague. Les SPNs qui sorat le plus sensibles 2 ces manipulations sont ceux dont la dCcharge a une composante qui est synchrone avec l'inspiration. 'Fous les SPNs de ce type qui ont i t6 testis, ont nlontrk une telle diminution. Leur riponse suit celle des motoneursnes phrkniques. 1 . e ~ SPNs qui sont le nloins sensibles sont ceux dont Be patron de dCcharge ne montre pas de modulation par la respiration. Seulement 12% des SPNs de ce type qui ont 6tk testis montrent Line diminution. Pour certains SPNs une suppression Glective par hypocapnke de l'activitk synchronide avec l'inspiration. met en Cvidcnse une dkcharge qui ne pcut i t re altCrCe par l'activation des recepteurs pulrnonaires affkrents sensibles B l'ktirement. Pour fin de comparaison, on a ktudie la rkponse rkflexe d'un m i m e tchantillon de SPNs i une augmentation de la pression artkrielle systCmiquc causke par l'injection intraveineuse de noradrknaline 45 &kg). La dkcharge de 84% des SPNs est diminuke pendant la piriode avant laquelle la noradrknaline a ajpl effet pressurisant. La friqucnce d'apparition des cffets dkpresseurs est similaire pour les SPNs ayant une rkponse rnodulCe par la respiration et ceux qui ne le sont pas. La dkcharge rksiduelle en hypocapnke des SPNs modulis par la respiration est kgalement diminuie. Ainsi la distribution dans cet ensemble de SPNs de la diminution des dkcharges CvoquCe

ABBREVIATIONS: SPN, sympathetic preganglionic neuron; SAP, systemic arterial pressure; PSR, pulmonary stretch receptor; CNS, central nervous system; NA. noradrenaline; CIA, central inspiratory activity.

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CAN. J. PHYSHBL. PHARMACOL. V8L. 56, 1978

par une augmentation de la pression artkrielle, contraste avec celle catnske par l'activation des rtccpte~ilrs pulmonaires affirents qu i sont sensibles B B'ktirement. Ces rksultats con- stituent une d6monstration direete de I'action dipressive sur Bes SPNs des rccepteurs pulnlonaires afferents sensibles B 1'Ctirement. Cette action avait auparavant fait l'sbjet d'ume hypothkse sur la base d'lane cvidence indirecte. Ee fait d'observer que 1':ictivation de ces Clkments adf6rents dirninue surtout la composante de la decharge des SPNs qiai est synchronisfe sur I'i~sspiration sbsggkre que l'effet est transrnis vers l'ensensblc de SPNs via le centre respiratoire.

[Traduit par le journal]

Introduction of air into the airways (Larrabee and Knowlton

Inflation c ~ f the lungs is known to cause a fall in SAP under experimental conditions which eliminate mechanical effects of the inflation on the clrcuPatlon (Brodic and Russell 1900; Salisbury et ul. 1959; Glick el a&. 1969) . Weak eiectrical stimulation of the intact vagal paalrnc~nary nerves evokes a similar effect, while section of the same nerves abolishes the depressor effect of lung inflation (Brodie a~nd Russell 1900). This phenomenon is therefore a reflex and is due to vasodilatation, consequent to a decrease in sympathetic tone (DaIy et a&. 1967; Daliy and Robin5on 1968). A set of analogies between the well-known inspiration-inhibitoq and expira- tion-excitatory reflcx of Hering and Breaner ( 1868 1, and the depressor reflex evoked by lung inflation ( Daly et a&. 1967), suggests that PSRs are respon- sible for tine reduction of vasomotor tone by lung inflati~>n. However, the CNS mechanism by which this depression of sympathetic tone is brought about has not been exyslai~~cd.

It is evcll established that lung inflation inhibits the activity of brainstern insplratory neurons (Coken 1969; Biarnchi and Barillot 1975). It has recently been shown that a large fraction of a SPN population receives an inspiration-synchrmus input as its main source of excitation (Preiss el 6al.

1975 1. The inspiration-synchrc~nous input is relayed to these SPNs by mechanisnns acting within the CNS. T!BUS, the possibility may be considered that lung inf ation leads to a decrease of sympathetic tone by its known inhibitory action on insparatory neuron activity, i.c., by a selective action on this particular cxcitaic~ry input to the SPW. The alternative posci- bility is that lung inflation exerts its depressant action on tine SPNs themselves or on antecedent facilitatory neaarons which relay respiratory-modu- Tated and nonrespiratory inputs to the SPNs.

The panrpcsse of the present study was to clarify the central mechanism of the depressant action of lung inflation on the sympathetic nervous system. The approach chosen was to study the effect of the Hering-Breuer inflation reflex on thc firing patterns of single SPNs. The following manocuvers werc used to elicit the reflex: injection of large amounts

1946; Bianchi and ~ a r j l l o t 1975 ; Russell and Bishop 1976), airway occ%usisn during the inflation phase of the cycle of artificial ventilation (Cohen 8 969) , and electrical stimulation of one cervical vagus nerve (Boyd and Maaske 1939). In addition to testing the hypotheses outlined above, thesc experiments have provided further information concerning the relationship between respiratory center activity and activity of an SPN pool. We have also compared the pattern of distribution, in the same preganglionic neuron pool, of the depressant effect evoked by lung inflation with that evoked by an elevation of SAP.

Our main finding is that SPNs with an inspiration- synchronous firing pattern are selectively depressed by the inflation reflex. This suggests that the under- Iying process acts predominantly upstream of the SPNs, probably by switching off a facilitatory input originating in the respiratory center. In contrast, the depression of SPN activity, reflexly caused by an SAP elevatic~n, is independent of firing pattern, suggesting that the underlying process acts eithcr on the SPN itsclf or on antecedent neurons which relay a11 tonic facilitatory inputs, both rhythmic and nonrhythrnic, tc~ the SPN.

Methods Cats were anaesthetized with Na pentobarbital ( 3 5 nag/

kg. ip) , paralyzed with gallamine triethiodide ( 8 mg kg R-'1, tracheostomi~ed and ventilated with a positive-pressure respiration pump. An artery and vein were cann~alated for recording SAP and for administering dr.tlgs. Bilateral pneumothsrax was performed in most cats. In 1 0 cats Qadequatcly hcparinized) SAP falls associated with lilng inflation were minimized by connecting the abdominal aorta t o a pressure stabilizer bottle. Body temperature was rnain- tained at 36-37°C by means s f a heating pad and infrared lamp. Tracheal pressure war measured via a needle inwrted into the trachea and connected to a Statham gauge. End- tidal C 0 2 concentration was monitored with a Beckman 12R2 analyzer and ventilation adjusted so as to obtain values between 3.5 and 4.5% (normocapnia), or I . and 2% (hypscapnia) .

The phrenic and cervical vagus nerves and \mall strands of the cervical sympathetic trunk were prepared and placed on bipolar silvcr hook electrodes in a pool of paraffin oil. The signals were amplified. displayed on a storage o5cilBo- scope. and recorded on magnetic tape. The phrenic nerve action potentials were half-wave rectified and integrated

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GERBER AND POLOSA 193

with a 'leaky' RC circuit (time constant 100 ms). In some cases, the SPNs' running average frequency was computed by a gated electronic pulse counter, the output voltage of which changed stepwise, in proportion to the number of input pulses accun~ulated over time increments, the value of which could be preset in the range 5.0 ms to 100 s.

The Hering-Breuer inspiratory-inhibitory reflex was evoked by lung inflation or by electrical stignulation of the cervical vagus nerve. Two methods were used to activate PSRs by inflating the lungs. With the first method, the respiration pump was stopped at the end of a deflation phase, the trachael tube occluded, and from 50 to 100 ml of air injected into the trachea with a large syringe. the plunger of which could be locked into position. With the second method, inflation was produced by manually closing a three-way valve in the tracheal tube. The inclusion of the valve in the airline did not increase the dead space. Inflation volumes greater than control were obtained by transient, graded occlusion of a siclearn1 of the tracheal tube during the inflation phase preceding valve closure. Most con~monly, inflation pressures 50% higher than peak control values were used, but sometimes vaIues up to two to four tirnes control were used. Control tracheal pressure values were 5 2 1.5 (SEM) mmHg at peak inflation, and atmospheric pressure at peak deflation. In 25 cats, direct electrical stimu- lation of PSR afferent fibers was achieved by applying trains of square pulses 0.1 ms in duration. at 80 Hz, to the cervi- cal vagus nerve. Stimulus intensity was two to four times the nerve threshold, actual voltages being 200-600 mV. Train duration was from 10 to 60 s. The stimulus intensity chosen, within this range, was that which caused an expira- tion of duration at least double the control value. This effect was obtained in 18 of the 25 cats tested. In seven of these, expiration persisted for as long as stimulation lasted. In the remainder, after the initial prolonged expiration, phrenic nerve activity resumed in spite of the continuing stimulation. An increase in stimulus intensity above that which caused a prolonged expiration usually resulted in inspiration- excitatory effects, characterized by the appearance of phrenic bursts of higher peak amplitude and frequency, presu~nably due to excitation of irritant and (or) chemo- receptor afferents. In 7 of the 25 cats in which vagus nerve stimulation was performed, no stimulus intensity was found which evoked a prolonged expiration.

Proof that PSR afferents were activated at the intensity of vagus nerve stimulation at which a prolonged expiration occurred was obtained with 'collision9 experiments. A stimulating electrode was placed on the vagals nerve close to the nodose ganglion. A recording electrode was placed on the same nerve as low in the neck as feasible (interelectrode distance, 6 cm). The latter electrode recorded bursts of action potentials associated in time with the inflation phase of the artificial respiration pump, that is, the firing of PSR afferents. 'The antidromic nerve action potential, evoked by a sti~nulus of intensity just suficient to cause a prolonged expiration. was attenuated in amplitude when it coincided in time with the firing of the PSR affesents. This observation suggests that collisions had occurred in PSK aflerents be- tween the antidromic and the orthcbdromic inflation-evoked action potentials and, therefore, that these afferents were being excited by the stin~uIatirtg electrode.

The possibility that the inspiration-inhibitory effects ob- tained by low-intensity vagal stimulation were due to excita- tion of baroreceptor afferents present in the vagus nerve is unlikely. Hn 15 of the preparations, the aortic nerve, which carries the bulk of the baroreceptos fibers originating from

the aortic arch (Hey~nans and Neil 19581, was isolated from the vagus and sectioned cranial to the stimulation site. When the cranial part of the aortic nerve was stimulated with the same s t imul~~s parameters which, when applied to the vagils nerve, caused a prolonged expiration, a fall in SAP, but only negligible changes in phrenic nerve activity. occurred.

NA (Levophed. Winthrop) was injected intravenously in doses of 5 pg/kg. This an~otrnt caused increases in SAP of between 463 and 108 mmHg.

'I'erms which will frequently be used in the text are defined below. Inspiration refers to the bursting phase of the phrenic nerve activity cycle. Expiration refers to the silent phase of the phrenic nerve activity cycle. Inflation and deflation refer to the two phases of the ventilation p u n ~ p cycle.

Results

Firing Patterns of SPNs during the Hering-Breuet. Inflati6ifz RejB'ex and Low-iretensity Vcpgus Nerve Sfbr?~ulation

A total of 47 SPNs were studied ixa 35 cats, in which lung inflation and (or) electrical stimulation of low threshold afferents in the cervical vagus nerve resultcd in complete suppression of phrenic nerve activity. These rnanoeuvers depressed the firing sf some SPNs, while having no effect on others. The effects of inflation on the SPNs were abolished by vagal section. When we exanlined possible causes for this variability we found that a relation existed between the firing patterns of tlae units in control conditions and the presence or absence of response to activation s f the lung inflation reflex. Therefore, we will describe separately bhe behaviour of units with different firing patterns.

First, we describe the behavioear of a group of 17 units which, in control coraditions, discharged a burst, a doublet. or a single spike onl~7 during in- spiration. During expiration, these units were silent. Because their firing pattern is reminiscent of that of inspiratory motoncurons, these units have been labelled "inspiratory" SPNs (Preiss et nl. 1975 ; Breiss and PoIosa 1977). Activation of the ir~flation reflex aboiishcd the activity of both plarcnic rnoto- neurons and inspiratory SPNs. The depressant effect had an identical tirne cotarse for both types of neurons. Of the 17 inspiratory SPNs, 9 were exam- ined during Iung inflation and 8 daring eHectrical stimulation sf the vagus nerve. Sixteen of the 17 units had the characteristic response described above. Examples are given in Figs. 1 and 2.

The one exception was a unit which, during eIec- trical stimulation of the vagus nervc And while phrenic nerve activity was completely suppressed, becamc silent initially and then began to fire without respiratory modulation for the whole duration sf stimulation. In this case, the firing appeared in asso-

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I

FIG. 1. Suppression of tiring of inspiratury SPN by electrical I stimulation of cervical vagus rmcrve. From top: stimulus signal, SB3N spikes, integrated pkrenlic neurograrn, SAP (catibraiion: 100 rnrnglg). Vagal stinnulation: 300 mV, 0.1 nas, 80 Hz for 30 s.

FIG. 2. Suppression of firing of inspiratory SPN by lung i ~ a f ation. Frorr~ top : tracheal pressure (increasing downward), SPN spikes, integrated phrenic neurogram, SAP (calibration: 100 mmHg). Time calibration: 10 s.

ciation with a decrease iam SAP. This tonic firing was tentatively interpreted as a secondary effect of the Hering-Breuer reflex, resulting froin reflex excita- tion of the SPN caused by the SAP drop.

In l~ypocapnia, the inspiratory SPNs became silent when phrenic nerve activity disappeared, with the exception of two units whose firing changed froin a respiratory-modulated to a nonnaodulated pattern. Lung inflation and vrtgal stimulation in hypocapnia were without effect on the silent units. One of the two units which became nonmodulated in hypo- capnia was tested again with electrical stimulation of the vagus nerve in this condition and likewise the sti~nulation had no effect.

In direct contrast with the behaviour of the in- spiratory SPNs is that of 16 SPNc whose control firing patterns showed no relationship to the phascs of the respiratory cycle (nonmodulated SPNs) . Thirteen of these units showed no changes in firing rate or pattern in response to activation of PSR

- Fire;. 3. Lack of effect of cervical vagus nerve stinlulation (A)

and Bung inflation (B) on firing CPP nonmodulated SPNs. Top record is stimulus signal in A, tracheal pre5sure (increasing downward) in W. Below, in A and B, are SPN spike\, integrated phrenic neurograrn, SAP (callbraeion: 100 mrnHg). Tlme calibration : 10 s.

afferents by lung inflation (eight units) or vagal stirnulation (eight units). Tlae activity of two units decreased while that of one unit increased during stimulation, but the average firing rate of the group, 1.5 -t- 1.3 (SEM) spikes per second, was un- changed. An illustration of this lack of response is presented in Fig. 3.

The insensitivity of these SPNs cannot be attrib- uted to weaker reflex effects of PSR aflerents in some cats, becausc in some preparations their stimulation abolished phrenic nerve activity and the activity of inspiratory SPNs. Sometimes it was possible to record the activity of both types of units si~iaultaneously, as in the case illalstratcd in Fig. 3A, in which the larger spikes are those of a nonmodu- lated SPN and the bursts of srnalIer spikes are from one inspiratory SPN or several. 'The different re- sponsiveness of these two populations of SPNs was stritistically significant ( p < 0.001, chi-square test).

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GERBER AND POLOSA

5 s

FIG. 4. E f i c t of lung inflation on SPN with firing pattern labelled as continuous with inspiratory peak. Normocapnia. From top: SPN spikes, ratemetcr record, phrenic neurogratn, tracheal pressure (increasing upward), SAP.

___*

5 5

FIG. 5. Lack of effect of lung inflation on firing of same neuron of Fig. 4 in hypocapnia (end-tital CO?, 2.07;). Records as in Fig. 3. Notice lack of respiratory modulation of SPN firing and also lack of efFect of lung inflation.

,4 third group of 11 SPWs showed a mixed re- sponse to activation of the lung inflation reflex. These neurons which discharge tonically at low frec~uency throughout expiration, and generate a burst of higher frequency firing during inspiration? have been labelled as "continuous with inspiratory peak" (Preiss et al. 1975). During sustained lung inflation or vagal stimulation, the inspiratory firing of these units ~7as lost and the units fired tonically without respiratory n~odulation (Fig. 4 ) . For the

unit shown in Fig. 4, the firing frequency was higher during inflation (as well as during hypo- capnia, see Fig. 5 ) than during expiration in control conditions. This is probably the consequence of the elimination of the period of postimpulse depression (Polosa 1967) associated with the inspiratory burst, during which this unit attained firing frequencies of 20-25 spikes/s.

The discharges of these units also Bost their respir- atory modulation when end-tidal 602 was lowered

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FIG. 6. Effect of cervical vagus nerve stimulation an firing of SPN with lowest firing probability in inspiration. From top: stimulus signal, SPN spikes, integrated phrenic neurograrn, SAP (calibration: BOO rnmHg). Time calibration: BO s.

by hyperventilation to the point where phrenic nerve activity disappeared (end-tidal COX B .5-2.0% ) . Under these conditions, lung inflation had m s effect on the firing sf the units (Fig. 5 ) .

Thus, only the inspiration-synchronous firing of these units was depressed by the inflatioil reflex.

Finally, a group of three SPNs which had a lower probability of firing during inspiratio11 than during expiration responded to lung inflation or electrical stimulation of the vagus nerve with a slight increase in their mean firing rate (Fig. 6 1.

Firing Patterns of SPNs during the Systemic: Arterial Pressure Elevation caused by Intravenous N A

Tlre data presented above show that the depres- sant effect of lung inflation is distributed in a char- acteristic fashion among an SPN population. It was of interest to compare the pattern of distribution, in the SPN pool, of the effects of the lung inflation reflex with those of the powerful inhibitory input activated by a rise in SAP. This is considered to originate predoininantly from arterial baroreceptors (Gernandt et a/ . 1946; Iggo and Vogt 1962). We tested the effect of a large SAP elevation, induced by intravenous NA on the firing of both inspiratory and nonmodulated SPNs. We also tested the effect of SAP elevation on the residual, llonmodulated firing, that some of the inspiratory SPNs exhibit at low end-tidal C02 levels. A total of 37 SPNs were studied in 25 cats. Twelve units were inspiratory, 10 continuous with inspiratory peak, the remainder, nonmodulated SPNs. The average increase in SAP was 50 mmHg (range from 40 to 100). The firing of 11 of the 12 inspiratory SPNs and of all 10 con- tinuoans with inspiratory peak SBNs was depressed during SAP elevation (Fig. 7A) . The peak ampli-

I %

FIG. 7. Depressant efrect of the systemic arterial pressure increase caused by intravenous noradrcnaline on thc firing of inspiratory SPNs. A and B show two different units. From top: SPN spikes, integrated phrenic neurogram, SA1' (caliba-a- tion: 100 mtnHg). Time calibration: 10 s.

te~de of the phrenic nerve bursts was also depressed in most instances. However, marked depression of inspiratory SPN firing occurred even when phrenic nerve activity was unaiIected, or only slightly de- pressed, by the SAP increasc (Fig. 7B). For some af these units, the test was repeated in hypocapnia. When phrenic nerve activity had disappeared, some units exhibited a residual, nonmodulated discharge which could be depressed by the SAP elevation (Fig. 8B). The nonmodulated SPNs were also sensitive to SAP elevation: the firing of 1 1 out of 15 was depressed (Fig. 8C). The observed difference in frequency of depressant eflccts in the two groups of SPNs was not significant ( p < 8.2, chi-square test). Unlike Seller (1 973), wc did not find units which increased their firing frequency during SAP elevation. We conclude that the depressant input activated by high SAP is distributed uniformly with- in an SPN pool, since it influences SPNs regardless of their firing patterns, in contrast with the selective distribution of the PSR effects.

Discussion

The present results provide a direct dernonstra- tion of the postulated depressant efTect of lung in- flation on SBN activity (Daly pi crl. 8967; Daly and Robinson 1968; Glick ei ale 1969). In addition, the results suggest that the depression of sympathetic activity evoked by lung inflation or weak elecfrical stimulation of the vagus nerve is due mainly to inhibition of an excitatory input to the SPNs, ratlmer than to a direct action on tlae SPN pool. The main reason for this inference is the observation that activation of the inflation rcflex invariablv depresses only the inspiration-synchrano~1s component of

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GERRER AND POLOSA

+----I

FIG. 8. nepressa~at effect of the SAP increase caused by intravenous NA on an SPN with csntinuous firing and inhpiratsry peak (A), on the residual firing of the sarne neuron in hypocapnia (B), and on the firing s f a raonrnodulated SPN (GI. Froin top: SPN firing, integrated phrenic neurogram, SAP (calibration: 100 n11nHg). Time calibration: 10 s.

SPN firing. Thus, if one assumes that the CIA is the generator of the inspiration-synchronous firing of SPNs, selective suppression of the inspiratory-syn- chronous firing of SPNs could only be achieved by turning off this generator. Support for this inter- pretation is provided by the observation that SPNs whose firing is sensitive to activation of the inflation reflex become insensitive when the CIA is sup- pressed by hypocapnia. This behaviour was shown by the one inspiratory SPN which was tested while firing tonically in hypocapnia and by all of the 11 SPWs which had contiiluous firing with inspiratory peak (Fig. 5 ) . An inhibitory input that impinged directly on the SPNs which also receivc the CIA should depress SPN firing independent of the level of CIA. Since there is no evidence that central trans- mission of the signals frona PSR is less effective in hypocapnia (Monteau et al. 1974), the lack of effect must be attributed to attenuation or suppres- sion of the CTA, which must, thercfore, be the neural substrate for the depressant acticjn of the PSRs. 'The characteristics of the depressant effect of barorecep- tor activation contrast sharply with those of the inflation reflex. The firing of all SPNs, regardless of firing pattern, is suppressed and the effect is inde- pendent of the Bevel of the CIA. This behaviour would be predicted for an input that projected directly to the SPN itself or to antecedent neurons which reIav all tonic facilitatory inputs to the SPN. Time fact that 2 of 16 nonmodulated SPNs could be depressed by lung inflation suggests that some connections between PSR afferents and SPNs, other

than those made via the respiratory center, may exist. This is in agreement with observations by Lipski et a&. (1977), who measured latencies of antidroinic invasion of single SPNs during lung inflation in expiration and found in some cases a slight lengthening. Similar conclusions were also reached by Gootman et al. (1977) who measured efferent activity of the whole splanchnic and cervical nerves during lung inflation and found that inflations performed during expiration depressed activity. Howevcr, the low incidence of this observation suggests that, in the conditions of our experiments, these connections may not significantly influence the output of this SPN pool.

Since our observations were limited to the SPNs projecting into the cervical nerve, they provide no answer to the important question of whether the described distribution pattern of the PSR afferent input is unique to the SPN population studied or is a property common to all SPNs.

These experiments have shown that the Hering- Breuer inflation reflex selectively depresses the fir- ing of inspiratory SPNs. Activity of inspiratory SPNs can also be depressed by hypocapnia (Preiss and PoIosa 1977) and by stimulation of the laryngeal nerve (unpublished), conditions which are known to depress CIA. Thus, the generalization can be made that the activity level of this fraction of the SPN pool will reflect faithfully thc activity level of brainstem inspiratory neurons, provided the influ- ence of other, nonrespiratory inputs, like the baro- receptors, is kept constant.

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Acknowledgments

This work was supported by a grant from the Medical Rcsearch Council of Canada. We thank Dr. I,askey for criticizing the manuscript.

BIAVVHI, A. L.. and RARILL~T, J . C. 1975. Activity of medullary respiratory neurons during reflexcs from the lungs in cat\. Respir. Physiol. 25. 335-352.

BOYL~, T. E., and ~ I A A S K F , C. A. 1939. Vagal inhibition of inspiratic~m, and accompanying ~ h i i n g c ~ in respiratcsry rhythnm. 4 . Neurophysiol. 2, 533-542.

WRODIE, T. G., and K u s s ~ r L, A. E. 1900. On reflex cardiac inhibition. J. Physiol. Ql-ondon), 26, 92-106.

COHEN, M. I. 1968. Discharge patterns of brainstem respira- tory neurons in relation to carbon dioxide tension. 9. Neurophy4iol. 3%. 142-1 65.

1969. D i ~ h a r g e patterns of brainstem respiratory ne~lrons during Hering-Brealer rcflex evoked by lung inflation. J . Neurophy4iol. 32, 356-374.

DALY, M. DE BURGH, HATZLEDHNF, J. E., and UWCAR, A. 1967. The reflex effects of alterations in Iring volalnne on systemic vascular resistance. J. Physiol. (London), 188, 33 8-351.

DAI Y. M. DF BURGH, and ROBINSON, B. W. 1968. An analy- sis of the reflex systcmic vasodilator re\ponse elicited by lung inflation in the dog. 9. Physiol. (London), 195, 387- 406.

GERNANDT, H.. ~ I L J E S T R ~ N ~ ) , 6.. and ZOTTFRMAN, Y. 8944, Efferent impulses in the splanchnic ncrvc. Acta Physiol. Scand. 11,230-247.

GLICK, G.. WECHSI FR, '4. S., and EPSTI IN, S. E. 1969. Reflex cardiovascular depression produced by stinnula- tion of pa~lmonary stretch receptors in the dog. 9. Clin. Invest. 48,467-473.

GOOTMAN, P. hf., FFLDMAN. 9. E., and COIIFN, M. 1. 1977 Pulmonary agerent influences on respiratory ~laodulatio~n of sympathetic discharge. Satellite syrnposium: Central interaction between respiratory and cardiovascirlar con- trol Systems. Berlin, 5 2-15, Bury 1977.

HERING. E., and BREUER, J. 1868. Self-steering of respiration

through the Nervrls Vagus. In Breathing. Ciba Founda- tion, Hering-Rretaer Centenary Symposium, 1970. B. 8: A. Churchill kid., London. pp. 359-394.

HEYMANS, C., and NHLII,, E. 1958. Reffexogenic areas of the cardisvasca~Iar system. J . Eli A. Churchill Etd., Eondon.

IGGO, A., and VBGT, M. 1962. The mechanisms of adrena- line-induced inhibition of sympathetic prepanglionic activity. J . Physiol. ( laondon), 16%. 62-72.

E~RRABEE, M. G., and KNOWI~ION, 6. C . 1946. Excit;~tii~n and inhibition of phrenic motorne~arons by inflation of the lungs. Am. J . Physiol. 147,961-99.

L,IPSKI, J., COOTE, J . H., and TR~FBSKI, A. 1977. Tear-epc~ral patterns of antidro~nic invasion latencies of sympathetic preganglionic neurons related to central inspiratory activity and pulmonary stretch receptor reflex. Brain Res. 135, 162-167.

%~ONTI.ALT, R., HILAIRE, G., and OUEDIPAOGC), C . 1974. COW- tribution a 1'Ctude de la fonction ventilatoire au cours de la polypnte therrnique on hypocapnique. J . Physiol. (Paris), 68, 97-120.

PAINTAH, A. S. 1953. The conduction velocities of respira- tory and cardiovascular afferent fibers in the vagu4 ncrvc. J . Physiol. (1-ondon), 121, 341-359.

POLOSA, C. 1947. The silent period of sympathetic prcgang- lionic neurons. Can. J . Physiol. Pharmacol. 45, 103.7- 1045.

PREISS. G., KIWCHNER, F., and P o k o s ~ , C. 1975. Patterning of sympathetic prcganglionic neuron firing by the central respiratory drive. Brain Res. 87, 343-374.

PIPI HSS, G., and Pot o s ~ , C. 1977. The relation bctwecn end- tidal C 0 2 :and discharge patterns of sympathetic pre- gangIionic neurons. Brain Wes. f 22, 255-267.

KUSSLLL, J . A., and BISHOP, B. 1976. Vagal afferents essen- tial for abdominal narnscle activity during lung inflation in cat& 8 . Appl. Physiol. 41, 3 10-3 15.

S41 lSRURY, P. It.'., GALEE'TTP. P. M., ~ ,EWIN, K. J . , and REEBEN, P. A. 1959. Stretch reflexel From the dog's liang to the systemic circulation. Circ. Res. 7, 62-67.

SELLER, PI. 1973. The discharge pattern of single units in thoracic and lumbar white rami in relation to cardio- vascular events. Pilhigers Arch. 343, 3 17-330.

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