Interaction of baroreceptor and chemoreceptor reflex control of sympathetic nerve activity in normal humans

Interaction of baroreceptor and chemoreceptor

reflex control of sympathetic nerve activity in

normal humans.

V K Somers, … , A L Mark, F M Abboud

J Clin Invest.

1991;

87(6)

:1953-1957.

https://doi.org/10.1172/JCI115221

.

Animal studies have demonstrated that activation of the baroreflex by increases in arterial

pressure inhibits cardiovascular and ventilatory responses to activation of peripheral

chemoreceptors (PC) with hypoxia. In this study, we examined the influences of baroreflex

activation on the sympathetic response to stimulation of PC and central chemoreceptors in

humans. PC were stimulated by hypoxia (10% O2/90% N2) (n = 6) and central

chemoreceptors by hypercapnia (7% CO2/93% O2) (n = 6). Responses to a cold pressor

stimulus were also obtained as an internal reflex control to determine the selectivity of the

interactive influence of baroreflex activation. Baroreflex activation was achieved by raising

mean blood pressure by greater than 10 mmHg with intravenous infusion of phenylephrine

(PE). Sympathetic nerve activity (SNA) to muscle was recorded from a peroneal nerve

(microneurography). During hypoxia alone, SNA increased from 255 +/- 92 to 354 +/- 107

U/min (P less than 0.05). During PE alone, mean blood pressure increased and SNA

decreased to 87 +/- 45 U/min (P less than 0.05). With hypoxia during baroreflex activation

with PE, SNA did not increase (50 +/- 23 U/min). During hypercapnia alone, SNA increased

from 116 +/- 39 to 234 +/- 72 U/min (P less than 0.01). Hypercapnia during baroreflex

activation with PE increased SNA from 32 +/- 25 U/min during PE alone to 61 +/- 26 […]

Research Article

Find the latest version:

Interaction

of

Baroreceptor

and

Chemoreceptor

Reflex Control

of

Sympathetic

Nerve

Activity in

Normal Humans

VirendK.Somers, AllynL. Mark, andFrancoisM.Abboud

DepartmentsofInternalMedicineandPhysiologyandBiophysics, Cardiovascular Center, UniversityofIowa, andthe Veterans Administration MedicalCenter,IowaCity,Iowa55242

Abstract

Animal studies havedemonstratedthat activation of the barore-flex by increases in arterial pressure inhibits cardiovascular andventilatoryresponses toactivation ofperipheral chemore-ceptors(PC)withhypoxia.Inthis study, weexaminedthe influ-encesof baroreflex activationon thesympatheticresponse to

stimulationofPCand centralchemoreceptors in humans. PC

werestimulatedbyhypoxia (10%

02/90%

N2) (n=

6)

and cen-tralchemoreceptorsbyhypercapnia(7%C02/93% 02) (n=6).

Responsesto a cold pressor stimulus were also obtained as an internalreflexcontrol todeterminetheselectivity ofthe inter-active influence of baroreflexactivation. Baroreflex activation was achieved byraisingmean blood pressureby>10 mmHg

withintravenousinfusion of phenylephrine (PE). Sympathetic

nerveactivity (SNA)to muscle was recordedfromaperoneal

nerve (microneurography). During hypoxia alone, SNA in-creased from255±92 to354±107U/min (P<0.05). During

PE alone, mean blood pressureincreasedandSNAdecreased to87±45 U/min (P<0.05). With hypoxia during baroreflex activationwithPE,SNAdid notincrease(50±23

U/min).

Dur-ing hypercapniaalone,SNA increased from 116±39to234±72 U/min (P<0.01). Hypercapnia during baroreflex activation

with PEincreasedSNA from32±25U/minduring PE alone to 61±26 U/min during hypercapnia and PE (P < 0.05). Like hypercapnia (but unlike hypoxia) thecold pressor test also in-creasedSNAduringPE.We conclude thatbaroreflex activa-tionselectively abolishestheSNAresponse tohypoxiabut not tohypercapniaorthe cold pressor test. Theinhibitory interac-tionof thebaroreflexand theperipheral chemoreflexmay be

explained byconvergence ofbaroreceptorandperipheral che-moreceptorafferentson neurons in the medulla.(J. Clin. In-vest. 1991.87:1953-1957.)Key words: hypoxia-

hypercapnia.

baroreflex*chemoreflex

Introduction

Baroreceptorandchemoreceptor reflexesexertconsiderable

in-fluenceonautonomiccontrol of the circulation, especially in situations

involving

stressors such asmarked changesinblood

pressure andinblood levelsofoxygen and carbondioxide.The

individual contributions of baroreflexesand theirresponsesto blood pressurealterationsandof chemoreflexesand their re-sponses tohypoxiaandhypercapniahave beenextensively

stud-iedin bothanimals(1,2)andhumans(3, 4).Thus far, however,

Addressreprintrequests to Dr.FrancoisM.Abboud, Departmentof InternalMedicine, University of Iowa College of Medicine, Iowa City, IA 52242.

Receivedfor publication 9July1990 and in revisedform 14 De-cember 1990.

The Journalof ClinicalInvestigation, Inc.

Volume87,June 1991, 1953-1957

interactionsofthese reflexes haveonlybeen studied in animals. Heistad et al. have shown in dogsthat baroreflex activation inhibits anddeactivationaugments theventilatoryresponseto

stimulation of theperipheral chemoreceptors

(5).

In

addition,

Mancia et al. have demonstrated that vasoconstrictor re-sponses toperipheral chemoreceptor stimulationareinhibited byelevation of bloodpressureand activation ofbaroreceptor

reflexes

(6).

Ithasbeen difficult to study the interaction ofbaroreceptor

andchemoreceptorreflexesin humansusingmeasurementsof vascularresistance and arterial pressure because the stimulito

these reflexes (vasoactive drugs andhypoxia) produce direct andconfoundingeffectsonthecirculation. However,withthe

useofmicroneurographic recordingsofsympatheticnerve

ac-tivity (SNA),' it is feasible to study the interaction of these reflexes in normal humans. We have shown that bothhypoxia

(peripheralchemoreceptorstimulation [7, 8]) and hypercapnia

(primarily central chemoreceptor stimulation [9, 10]) trigger

increasesinSNA in humans(4). Furthermore,baroreflex acti-vationinhibits SNA. We, therefore, examined the effect ofbaro-reflex activation(elevationof systemicpressureusing

intrave-nousphenylephrine infusions)onsympatheticnerve responses tostimulation ofperipheralchemoreceptors (by hypoxia), to

stimulationofcentral chemoreceptors (byhypercapnia),andto acoldpressorstimulus(usedas aninternal reflexcontrol).

Methods

10 normal human volunteers (7 male, 3 female) aged 24±3 yr were studied. All were nonsmokers and receiving no medication. Measure-ments were takenof heart rate (EKG), breathing patterns (pneumo-tach), blood pressure (Physio-Control Lifestat 200 semiautomated sphygmomanometer; Redmond, WA), 02 saturation (Nellcor N-l 100 Cpulseoximeter, Hayward, CA), end tidal CO2 (472 1OA capnometer; Hewlett-Packard Co., Andover, MA), central venous pressure, and sympathetic nerveactivity to muscleusing microneurography (11). SNAwasmeasureddirectlybyinsertingatungstenmicroelectrode into a nervefascicle tomuscle in the peroneal nerve. Sympathetic bursts wereidentified by inspection of the mean voltage neurogram and sym-patheticactivity was calculated as bursts/minXmeanburst amplitude andexpressed inarbitrary units (12). We also measured minute venti-lation usingaventilation monitor (LS-75; Bourns, Riverside, CA).

Subjectswereexposedtogasmixtures intendedtoinduce either hypoxia (10% 02, 90% N2) or hypercapnia (7%CO2,93%02)- Subjects underwent measurement of baseline variables for 3 min while breath-ingroomair. Then using a three-way valve, the subjects were exposed toeither the hypoxic (six subjects)orhypercapnic(sixsubjects) stress-orsfor 5 min. Average values forthe5-minperiod ofgas exposurewere usedin the comparisons.Inonesubject, responses to hypercapnia with andwithout phenylephrine (PE) were obtained over 3 min because of

1.Abbreviations usedinthispaper:CPT, cold pressortest;CVP, central

venous pressure; MBP, mean blood pressure; SNA, sympathetic nerve

activity; VE,minute ventilation.

inability to comfortably tolerate the stress for a longer period. Note that responses tohypoxiawith and without PE were obtained in six subjects and tohypercapniawith andwithoutPEinsixsubjects.Twosubjects underwentboth protocols (on separate days) and provided data for both thehypoxic as well as the hypercapnic stimuli. Exposuretoeach of the gasmixtureswas performedin the baselinestateand during

elevation of systemic pressure usingan intravenousinfusion of PE.

InfusionofPEwastitratedtomaintainmeanblood pressure (MBP) at 210 mmHg above baseline (thereby activating thebaroreflexes).The

interventionsincluded: (a) hypoxia or hypercapnia alone;(b)PEalone; (c)hypoxia orhypercapnia duringphenylephrineinfusion.Theorder of the interventionswasrandomly allocated. At least 30 min separated the endofoneintervention from thebeginningofthe next. Exposure to gas mixturesduringthePEinfusionswasperformed only aftera con-stantinfusionof PE for at least 10 mintoensureasteadystate.

Duringhypoxia, hypocapniasecondary to thehyperventilationwas avoided bytitrating CO2tomaintainisocapnia.

Weexamined the effects of hypoxia and hypercapniaonSNA and compared theseeffectstothose recorded when thebaroreflexeswere

activated duringthe PEinfusion.Infour subjects,wefurtherexamined theeffects of the cold pressortest(CPT)onSNA both in the baseline state aswellasduringthe PEinfusion. The CPTwasperformed by

havingsubjects insert their hands to a predetermined depth into a

con-tainerof ice for 2 min.

Theeffectsof hypoxia,hypercapnia,andthe CPT during the base-line state were compared with their effects during baroreflex activation

(bythe PEinfusion) usingtheWilcoxon'ssignedrank test. To assess minute by minute changes in the measuredvariables,the data were

furtheranalyzedusingarepeated measures one-way analysisof vari-ance(TableIII). Significancewasassumedatthe 5% level. Valuesare expressedasmean±standarderror.

Thestudywasapprovedby theUniversityofIowa HumanSubjects

ReviewCommittee,and eachsubjectgaveinformedwrittenconsent.

Results

(I)

Effects of

hypoxia

(Table

I)

(a) On baseline

variables. During hypoxia, 02

saturation fell from 99±0.4% to 83±1.4% (P < 0.05), with an increase in minuteventilation

(Vs)

from 6.7±0.7to 1

1.8±1.0 liters/min

(P

<0.05) (TableIII), and an increase in SNA from255±92to

354±107 U/min (P<0.05).MBPand centralvenous pressure

(CVP)did notchange.

(b)

During

phenylephrine. During

PE

alone,

MBP in-creasedby - 10 mmHg (P<

0.05)

and heartrateslowed

by

- 11 beats/min (P< 0.05). CVP

increased

from 0.7±0.5 to

Table L ComparisonofEffectsofHypoxia Alone andduring Phenylephrine Infusion

Hypoxia

Baseline Hypoxia Phenylephrine +phenylephrine

02Sat(%) 99±0.4 83±1.4* 99±0.5

84±1.8*4

PCO2

(mmHg)

41±1.3 40±1.3 40±1.8 41±1.4

MBP(mmHg) 80.0±3.6 80.3±3.9

89.7±2.3*0

93.0±3.5*1

HR(beats/min) 65.8±2.4 83.2±4.4*

54.5±3.1*1

65.7±4.3#

CVP(mmHg) 0.7±0.5 0.3±1.0

2.7±1.0*1

3.3±0.9*0

VE

(liters/min) 6.7±0.7 11.8±1.0*

7.i±0.81

10.8±0.8**

SNA(U/min) 255±92 354±107* 87±45§ 50±23*§

n=6.*P<0.05 comparedtobaseline;tP<0.05comparedto PE

alone;§P<0.05 comparedtohypoxiaalone.

Conltro

SNA

RESP

PE

SPA

Hypoxia

PE .

PE+_Hypoxba

Figure

1.

Recordings

of

sympathetic

nerve

ac-tivity (SNA)

and

respi-ratory

tracings

(RESP)

ina

_single

_subject,

at

baseline

(control;

top

left), during hypoxia

(top

right), during

PE

infusion

(bottom left),

and

during

the combi-nation of

_hypoxia

and PEinfusion. Expirationisindicated byupward movement of the

re-spiratorytraceand inspiration by downward movement. Note that

hypoxiaalone increasedSNA,whereas PE suppressed SNA. Most

importantly, hypoxia duringPEresulted in aslight further suppres-sion of SNA.

2.7±1

mmHg (P

<

0.05).

VE

did not

change,

but SNA fell

strikingly

from327±132to87±45

U/min (P

<

_0.05).

With

hypoxia

during PE, MBPwas93±3.5 mmHg (- 13

mmHg

greater thanduring hypoxia alone) (P<0.05).

How-ever, 02 saturation

(84±1.8%)

and

VE (10.8±0.8

liters/min)

weresimilartovalues during hypoxiaalone(Table III).With

addition of

hypoxia during PE,

SNA failed to increase and indeed tended todecreaseeven further than levels recorded

during

PEalone

(87±45

to50±23

U/min) (Figs.

1 and

2).

(II)

Effects ofhypercapnia (Table

II)

(a)

On baseline variables.

During

hypercapnia, end tidal

CO2

increasedfrom40±2.7 to53±1.5 mmHg (P<0.05), withan

increasein

VE

from 6.7±0.6to19.2±2.4 liters/min (P<

0.05)

(Table III) andan increase inSNA from 116±39 to234±72

U/min

(P<0.05). MBPincreasedfrom76.5±3.1to82.3±3.1 mmHg

(P

<0.05) and CVP increased from 0.8±0.6to1.8±0.4 mmHg (P<

0.05).

(b)

During phenylephrine. During

PE alone, MBP

in-creased to 84.7±2.3 mmHg

(P

<0.05), heart rateslowedto

55.0±5.1 beats/min (P<0.05), and CVPincreasedto3.2±0.6

Minute

_Figure

_2.

_Group

_data

MSNA ventilation

(units/mitt) (Imin) for sixsubjects showing

2.0 . theeffects ofhypoxia

35

m

_105(H),

_{phenylephrine}

alone (PE), andhypoxia

300- .9.0- duringPE(PE+H)on

sympathetic

nerve

ac-250- T tivity (SNA; left) and

200- 6.0- minuteventilation

(right), as compared to

50- C,4.5_ measurements recorded

..

t~h-

NS

,1.

3.0_

_-..

,.

.

'Note

in thecontrol (C)state. that

_hypoxia

in-creased SNA and

venti-MOP

~

~ ~ ~~~~ ~

lation. PEmarkedly

suppressed SNA.

Hyp-C H PEPE. C H PEPE4H *

MBP 8t 8290 93

oxia

duringPE resulted

(mmo~g)

_in

_no

_increase

_(and

in-deedatendencytoa

decrease) in SNA. Baroreflexstimulationby PE,however,did not significantly reduce the ventilatory response to hypoxia. Shownatthe bottom of the left panelarevalues for MBPduringeach of the inter-ventions. (*P < 0.05).

Table II. Comparison ofEffects ofHypercapnia Alone

and during Phenylephrine Infusion

Hypercapnia Baseline Hypercapnia Phenylephrine +phenylephrine

02 Sat (%) 99±0.4 100±0.0 99±0.4 100±0.0

PCO2(mmHg) 40±2.7 53+1.5* 41±1.4 55±0.5*t MBP(MmHg) 76.5±3.1 82.3±3.1* 84.7±2.3* 93.7±1.7*tf

HR

('beats/min)

67.2±5.7 71.2±6.5 55.0±5.1* 61.3±4.7§

CVP(mmHg) 0.8±0.4 1.8±0.4* 3.2±0.6* 5.2+0.7*$§

VE

(fliters/min)

6.7±0.6 19.2±2.4* 5.7±0.6

20.2±1.8**

SNA(U/min) 116±39 234±72* 32±25* 61±24**1

n=6.*P<0.05 comparedtobaseline; tP <0.05 comparedtoPE

alone;I_{P <0.05 comparedtohypercapniaalone.}

mmHg (P <0.05). VE didnotchange. SNA fellto 32±25

U/

min (P <0.05).

With hypercapnia during PE, MBP rose to 93.7±1.7

mmHg (- 11 mmHg greater thanduring hypercapnia alone) and CVP increased furtherto5.2±0.7 mmHg(P<0.05).

De-spite the increasein MBPandCVPwith the addition of

hyper-capnia,

SNA almost doubled(from 32±25to61±24 U/min;P

<0.05).

YE

(20.2±1.8 liters/min) and end tidal CO2 (55±0.5 mmHg)were similartolevels recorded during hypercapnia alone(Table III; Figs. 3 and 4).

(III)

Effects

ofthe cold pressor test

(a)

On

baseline variables. CPT increased

MBP

(from 77±1.9

to90.5±5.9;P<0.05) and SNA (from 162±40to514±182;P

<0.05).CVP and

VE

didnotchangesignificantly.

(b)

During

phenylephrine.

CPTduring PE resulted in a

fur-therincrease in MBPfrom 91±3.2 (PE alone) to 107±6.4 mmHg (P < 0.05). CVP was 5.2±0.5 during CPT alone,

5.7±0.5 duringPE alone, and 5.7±0.8 withCPTduringPE.

Despite the increase in MBP with CPTduring PE, SNA in-creasedfrom5.5±1.9 U/min during PE alone to 285±128

U/

min

during

CPTand PE(Fig.5).

Discussion

Themajornewfinding in this studywasinhibition of the

sym-patheticnerveresponsetohypoxia (peripheral chemoreceptor stimulation) by baroreceptor activationinhumans.

Astrength ofthis studywasthe directmeasurementof

sym-patheticnerveactivity using microneurography. This enabled ananalysis of these reflex interactions by providingameasure

of the efferent sympathetic neural response to simultaneous activation of both baroreceptor and chemoreceptor afferents thatisnotinfluenced by direct effects of hypoxia, hypercapnia, andphenylephrine.

Alimitation of the studywasthe fact that theuse

ofphenyl-ephrinetoactivatebaroreceptors raises centralvenouspressure

aswellassystemic arterialpressure.Hence it isnotpossibleto

distinguish whether the interactions evidentaredueto activa-tion of arterial baroreceptorsorofcardiopulmonaryreceptors orboth. In addition, wehavenotinthisstudy examined the effectsofbaroreflex deactivation onthe chemoreceptor re-sponses.

A possible criticism is that the use of phenylephrine (an

alpha agonist and thereforea vasoconstrictor)toactivate the baroreflexmaybeassociated with direct effects of phenyleph-rine (independent of the effects of the increased arterial

pres-sure)onthe chemoreceptors. If thiswereso,and

vasoconstric-tionoccurred in the chemoreceptors,wewouldexpectan

aug-mentation rather thananinhibition oftheresponsetohypoxia, since vasoconstriction would increase the hypoxic stimulus. Furthermore, intravenous infusions of norepinephrine

in-crease,ratherthandecrease the respiratoryresponsetohypoxia inman(13). Inanyevent,anyeffects ofphenylephrineonthe baroreflex itself is unlikely to have influenced our findings,

sinceanysuch effect would bepresentduring both the hypoxic andhypercapnicstresses. Withregardtopossible effects of

phenylephrineonthebaroreflexes, the doses ofphenylephrine

used in thisstudy donotsensitize the arterial baroreceptorsto

graded levels of neckpressure(14).

We have confirmed earlier human studiesdemonstrating

sympathetic neural activation by both hypoxia and

hypercap-TableIII.MinutebyMinuteChangesin02 Saturation, EndTidal C02, and VentilationduringHypoxiaandHypercapnia

with and withoutPhenylephrine

Baseline Minute 1 Minute 2 Minute 3 Minute 4 Minute 5

Hypoxia(n=6)

02

Sat(%) 99±0.4

89±1.9**

85±1.0** 83±1.3* 80±2.1* 78±2.4*

VE

(liters/min)

6.7±0.7

9.8±1.0*

11.4±1.0*t 12.5±1.4* 13.3±1.1* 12.8±1.2*

Hypoxia+PE(n=6)

02Sat(%) 99±0.5 92±1.5*t 84±1.4** 82±2.5* 79±1.5* 77±2.5*

VE

(liters/min)

7.1±0.9

9.1±1.0*4

10.6±1.1I 11.7±0.7* 11.8±0.6* 11.6±0.7*

Hypercapnia (n=5)

PCO2 (mmHg) 42±0.8 53±1.0** 54±1.0* 55±1.1* 56±0.7* 56±0.7*

VE

(liters/min)

6.3±0.6

11.5±1.3*4

17.8±2.6*t 19.0±2.2* 24.3±3.3* 26.1±3.4*

Hypercapnia + PE (n=5)

PCO2

(mmHg) 42±0.8

53±1.0**

54±1.0* 55±0.6* 56±0.5* 56±0.4

VE

(liters/min)

6.7±0.7

_12.0±1.1*$

19.0±1.8**

23.0±2.2* 25.4±2.6* 26.7±2.6*

*_{P <0.05 compared to}

_baseline;t

_{P <0.05 compared to the previous minute.}

₀₂

Sat, oxygen saturation. Note: The

02

saturation and venti-latory responses over timeforhypoxia alone and hypoxia and phenylephrine were similar, as were thepCO2andventilatory responses over time forhypercapniaaloneandhypercapniaandphenylephrine.

Figure 3. Recordingsof sympathetic nerve

ac-tivity (SNA)and

respi-ratorytracings(RESP) inasingle subject, at

baseline (control;top

left), hypercapnia (top right),during PE infu-sion(bottom left), and during hypercapnia im-posed during PE infu-sion. Note that hyper-capnia alone increased SNA, andPEsuppressed SNA. However, de-spitethe suppression by PE, superimposed hypercapnia (unlike hypoxia) still elicitedasubstantialSNAresponse.

nia.More importantly, in this studywehave shown in humans

thatbaroreceptoractivation inhibits the sympatheticresponses tohypoxia. Thisbaroreceptor-chemoreceptorinteractionwas

previously described in animals (5, 6, 15, 16). In humans, this interaction appearstobespecific for hypoxia, which activates primarily peripheralchemoreceptors.Incontrast,during baro-reflex activation, sympatho-excitation still occursduring

hy-percapnia,which stimulates primarily centralchemoreceptors.

Sympatho-excitation is also present in response toa potent

nonspecificstimulus suchasthe coldpressortest.This specific-ity ofthe interaction between the baroreceptors and the periph-eral(butnotcentral)chemoreceptorsis remarkably similarto aninteraction thatwereported earlier where ventilation (and

thereby activation of thoracic afferents) inhibited the

sympa-theticresponsetohypoxia farmoreprofoundly than it

inhib-ited the sympathetic response to hypercapnia (4). These

se-lective interactions may be explained by neurophysiological studies demonstrating that carotid baroreceptor and

chemore-ceptorneurons aredistributedincloseproximityinthesolitary and paramedian reticular nucleiinthe medulla, such that

in-terneuronal connections mightfacilitate interactions between

these reflexes (17).

Minute Figure4. Group data

MSNA Ventilation

(unitsilmin) (1/min) for six subjects showing

theeffects of hypercap-nia(C02),PEalone

255 20- X _(PE),andhypercapnia

.

duringPE(PE+C02), . showing sympathetic

nerveactivity (MSNA; left) and minute

ventila-tion(right),as

com-paredtothe

measure-mentrecorded in the

CO CCOOE control(C)state.

Hy-MP 7782 85 94 percapnia increased

(mmHg)

both SNA and

ventila-tion. Despitethemarkedsuppressionof SNAby PE,hypercapnia duringPEstillelicitedanincrease inSNA,unlike thecomplete

sup-pressionseenduring hypoxia (Fig. 2).Baroreflex activationbyPEdid notinfluence theventilatoryresponsetohypercapnia.Values for

MBPobtainedduringthe various interventionsareshown below the

figureontheleft.

Contro

SNA

RESP

PE

sd _

REW

WIr _Figure

_5.

_Recordingsof sympatheticnerve ac-tivity (SNA) and

respi-ratory

tracings (RESP)

inasinglesubject,at

row baseline(control; top

PE Orr _left),duringthe cold ~~A~~lA pressor test(CPT;top

~ right), duringaPE infu-sion

_(bottom

_left),

and

duringtheCPT

im-posed duringthe PE in-fusion. Baroreflex acti-vationby PE didnotabolish the SNAresponsetoCPT (compare the

responsetohypoxia in Fig. 1).

Anunexpectedfindinginthis studywasthatSNAtendedto

decrease(not increase)whenhypoxiawasimposed

during

baro-receptoractivation withphenylephrine. Activation ofthe

baro-reflexmayexplain the failure of SNAtorisewhenperipheral

chemoreceptorsarestimulated by hypoxia, but whywould

SNA tendto decrease? There aretwo possibleexplanations.

First, when hypoxiawasimposed during PE, therewas aslight

increase in bloodpressurewhich would produce further

barore-flex inhibition of SNA. Second, when hypoxiawas imposed

during PE, therewas an increase in ventilation which could

inhibit SNA by activating thoracic stretchreceptors.

We didnotsee aninhibitory influence ofbaroreceptor

acti-vationonthe ventilatoryresponsetohypoxia,ashas been

re-ported in animals (5). Thismaybeexplained by the fact that the magnitude of thepressurechange in animal studies (> 100

mmHg) far exceeded thepressureincrease in this study (- 10

mmHg). The significance of this absence ofany ventilatory

inhibition despite sympathetic inhibition is that thebaroreflex

chemoreflex interaction may more profoundly influence the sympathetic limb of the chemoreflexascomparedtothe venti-latory limb.

The results of this study shed lightonourearlierreportof sympathetic hyperresponsivenesstohypoxia in borderline hy-pertensives (18). We speculate that the barorefleximpairment

known tooccur in hypertension, may result ina loss of the

inhibitory tonicor restraining influence of baroreceptorson

theexcitatoryeffect ofchemoreceptors during hypoxia.

In conclusion, these data demonstrateaspecific interaction

between baroreceptors and peripheral chemoreceptors in

regu-lation of sympatheticnerveactivity in normal humans. Activa-tionofbaroreceptorsby increases in arterialpressurewith

phen-ylephrinemarkedlyinhibit thesympatho-excitatory response

tostimulation of peripheralchemoreceptorswith hypoxia. Thisinhibitory influence of baroreceptor activation wasnot

observed during stimulation of central chemoreceptors with

hypercapnia.

Acknowledgments

The authors wishtothankMary Clary for'experttechnical assistance andNancy Stampfortypingthemanuscript.

The workwascarriedoutwithsupportof grantsHL-24962 and

HL-14388 from the NationalHeart,Lung,and BloodInstitute ofthe National Institutes of Health.

1956 V. KSomers,A. L.Mark,and F. M. Abboud ConW

SNA

RESP *~<P

PE

IHypwcapnla

.. Hy.pecp PE+_Hypepnis

SNA

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2. Walker,B. R.,and B. L. Brizzee. 1990. Cardiovascularresponsestohypoxia

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