Interaction of Cardiopulmonaryand Somatic Reflexes in Humans

JOHNL. WALKER, FRANCOIS M. ABBOUD, ALLYN L. MARK, and MARCD. THAMES,Cardiovascular Division, Department of Internal Medicine,Department of Physiology, and Cardiovascular Center,University of Iowa College of Medicine, Iowa Citi, Iowa 52242

A B S T R A C T Activation of cardiopulmonary re-ceptors with vagal afferents results predominantly inreflex inhibition of efferent sympathetic activity,whereas activation of somatic receptors reflexly in-creases sympathetic activity to the heart and circula-tion. Previous studies in experimental animals indicatethat there is an important interaction between theseexcitatory and inhibitory reflexes in the control of therenal circulation.

The purpose of this study was to determine whetherthere is a similar interaction between somatic andcardiopulmonary reflexes in humans. The activity ofthe cardiopulmonary receptors was altered (reduced)with lower body negative pressure (-5 mmHg), whichcauses a decrease in cardiac filling pressure and a smallreflex increase in forearm vascular resistance withoutaccompanying changes in arterial pressure. Activationof somatic receptors by isometric handgrip for 2 min at10 and 20%of maximum voluntary contraction restultedin reflex vasoconstriction in the nonexercising arm.Lower body negative pressure at - 5 mmHg produced athreefold augmentation in the forearm vasoconstrictorresponse to isometric handgrip in the nonexercisingarm. This increase in resistance was significantlygreater (P < 0.05) than the algebraic sum of theincreases in resistance resulting from lower bodysuction alone plus isometric handgrip alone. Further-more, it occurred despite a greater rise in arterialpressure, which would be expected to decrease foreairmvascular resistance through activation of arterial

This paper was presented in part at the National Meetingof the American Federation for Clinical Research, Washing-ton, D. C., May 1979.

Dr. Walker was a recipient of' a National Institutes ofHealth traineeship. Dr. Thames is the recipient of a ResearchCareer Development award from the National Heart, Lungand Blood Institute.

Received for publication 2 July 1979 and in revised form4 January 1980.

baroreceptors and through passive dlilatation of forearrmvessels. Thus, removal of the inhlibitorv infltuenice ofcardiopulmoniary receptors by pooliing 1)lood0 in thelower extremities enhanices the soimiatic reflex. Thesedata suggest an interaction l)etween cardliopulm ionarvand somatic reflexes in the control of forearrm vascularresistance in man.

INTRODUCTIONActivation of cardiopulmonary receptors with vagalafferents reflexly inhibits sympathetic adrenergicdischarge to mnany vascular beds in animals and humans(1-6). Conversely, activation of somatic receptorstriggers excitatory reflex responses as a result ofincreased symipathetic adrenergic discharge (7-10).Exercise is a potent stimulus to somatic receptors anidresults in reflex increases in heart rate, meian arterialpressure, and systemic vascular resistance (8, 11, 12).The effects of exercise on cardioptlmiioniary receptorsare less well-defined but the increase in ventricularcontractility and stroke voltumiie wouil(d be expected toaiugment the discharge of' cardlioptl m)oniarv receptorswith vagal afferents (13, 14) anid, thuis, reflexlv inhibitsympathetic ouitflow to the resistaniee vessels (14).Interactions letween the inhibitory car(lioptlll moniaryreflex andl the excitatory somlatic reflex may, therefore,play ain imnportanit role in the neuiral conitrol of' thecirculation (lutring exercise.

In the dog, there is an important interaction amongsomatic, sinoaortic, and cardiopulmonary (vagal)reflexes (15-17). The reflex renal vasoconstrictorresponse to stimulation of somatic afferents wasmarkedly augmented after removal of the tonic inhibi-tory influence of cardiac vagal afferents on the sym-pathetic system (17). Conversely, the somatic reflexwas inhibited after activation of the cardiopulmonaryreceptors by volume loading (17). The purpose of thepresent study was to determine whether an initeractionbetween the somatic and cardiopulmonary reflexes

J. Clin. Invest. ( The American Society for Clinical Investigation, Inc. 0021-9738/80/0611491/07 $1.00Volume 65 June 1980 1491-1497

1491

is present in humans. The results show that theincreases in forearm vascular tone, observed withisometric handgrip, are markedly potentiated byreducing the stimulus to the cardiopulmonary re-ceptors with low levels of lower body negativepressure (LBNP).1

METHODS

11 healthy males, 21-33 vr, were studlied. The studlies were(lone with the suhject lying supine in a warm (26°C) quietroom. The lower body was enclosed in an airtight box to thelevel of' the iliac crests. Low levels of' LBNP have beenpreviously shown to decrease the tonic inhibitory influencef'rom receptors in the calrdiopulmoniarv area without changingarterial bloo10 pressure andl to result in a dlecrease in forearmllblood flow (5, 6). Blood flow to the right forearmii was meassuredwith a Whitney mercury-in-silastic strain gauge plethysmo-graph (18). The strain gauge was placed around the f'orearm,4-8 cm distal to the elbow. The arm was elevated andsupported at the wrist so that the proximal forearm was - 10 cmabove the anterior chest wall. A pneumatic cuff was placedaround the upper arm and inflated intermittently abovevenous pressure for 6-8 s. To exclude the circulation to thehand, a seconid cuff applied to the wrist was inflated to supra-systolic pressures during the measurements. Forearm bloodflow was calculated f'rom the rate of' increase of f'orearmvolumiie during venous occlusion and expressed as millilitersper minute per 100 ml forearm volume. Arterial blood pressurewas dletermined by sphygmomlanometry f'rom the left arm.One of' us, J.L.W., performed all the blood pressure deter-minations to eliminate interobserver variation. Mean arterialpressure was calculated by adding one-third of the pulsepressure to the diastolic pressure. Forearm vascular resistancewas calculated by dividing mean arterial pressuire in mil-limeters of Hg by forearm blood flow.

Somatic receptors were stimulated by isometric handgrip.Each subject squeezed a handgrip dynamometer (Westondynainomneter; Weston Instruments, Inc., Newark, N. J.) tothe maximal force he could develop with the left hand. Thismeassuremenit was taken as the subject's maximal voluntaryconitraction (MVC). Subjects were then asked to maintain atension of 10 and 20%of their MVCfor 2 min. Care was takento insure that the subjects did not perform a Valsalva maneuverduring the 2-min periods of' handgrip exercise. In addition,the subjects were trained to avoid contracting the musclesof' the nonexercising arm. The magnitude of the response toexercise was determined by the degree of vasoconstrictionobserved in the nonexercising right forearm.

In four subjects, central venous pressure was continuouslymeasured with a cannula (60 cm long, 0.7 mmi.d.) insertedinto an antecuibital vein and advancedl into an intrathoracicvein.

Heart rate was determined in all subjects by continuouselectrocardiograims recorded at 2.5 mm/s.

The changes in mean arterial blood pressure, heart rate,forearm blood flow, and forearm vascutlar resistance, whichrestulted from isometric handgrip alone, were compared withthose that occturred when the exercise was performedduring LBNP.

Protocol. The study protocol was approved by the HumanStudy Committee of' the Uniiversity of' Iowa College of

1 Abbreviations used in this paper: LBNP, lower bodynegative pressture; MC\', m-aximal voltuntary contraction.

Medicine, and informed written consent was obtained fromall subjects.

Recordings were made during the following interventions:(a) LBNPat -5 mmHg, (b) handgrip at 10% MVC, (c) hand-grip at 20% MVC, (d) handgrip at 10% MVCplus LBNP at-5 mmHg, and (e) handgrip at 20% MVCplus LBNP at -5mmHg. The order of these five interventions was randomized.Each study period lasted 6 min, incluiding 2 min each ofcontrol measurements, measurements during interventioni,and recovery measurements. There was a 5-min rest periodlbetween each 6-min stuidy period. Forearm blood flow andlheart rate dleterminiiations were m-ade between 30-90 s of'each 2-miml interval; blood pressture was determinedlbetween 60-90 s.

Data analy sis. Statistical comparisons were made withthe t test for paired observations or by analysis of variance.Values of' P < 0.05 were considered significant. Results areexpressed in the figures and text as; mea-+-1 SE.

RESULTS

Effect of LBNP (-5 mmHg). During LBNP at-5 mmHg, central venous pressure decreased by1.5-2.5 mmHg in the 4 of 11 subjects in whom it wasmeasured. This low level of LBNP produced a smallincrease in the forearm resistance without significantlyaltering systemic arterial pressure (Table I). There wasno reflex tachycardia; in fact, a slight but significantdecrease in heart rate was noted.

Effect of isometric handgrip exercise. Table I andFigs. 1 and 2 show that handgrip at both 10 and 20%of MVCproduced no significant change in calculatedforearm vascular resistance, but there were significantincreases in arterial pressure and heart rate. Therewas no change in central venous pressure with iso-metric handgrip at either 10 or 20% of MVC. Theincreases in heart rate and arterial pressure weregreater during handgrip at 20% than during handgripat 10% of MVC.

Effects of LBNPon responses to handgrip. Table Iand Fig. 2 show that LBNP caused a greater thanthreefold increase in the forearm vasoconstrictorresponse to handgrip at 10 and 20%of MVC, an increasein the arterial pressure response at 20% of MVC, butdid not alter the heart rate response. The increases inresistance and arterial pressure were greater than thealgebraic sum of the increases for each interventionalone. The decrease in central venous pressure wasunchanged from that observed with LBNP alone.

DISCUSSION

The data indicate that the reflex vasoconstrictorresponse to isometric handgrip is markedly augmentedduring LBNP. The augmentation of the response wassignificantly greater than the simple algebraic sum ofthe vasoconstriction caused by LBNP alone plus thatcaused by isometric exercise alone. These resultsare consistent with the view that LBNPreduced a tonicinhibitory influence of cardiopulmonary receptors on

1492 J. L. Walker, F. M. Abboud, A. L. Mark, and M. D. Thames

TABLE IEffects of LBNPand Isometric Handgrip with and without LBN Pressure

Mean Forearmarterial Forearmii vascular

Heart rate pressure blood flow resistance

beatshnin mnmti Hg ml/miri/IOO ?111mlrm Hg/mlnmiin/1OO rnl

Effect of LBNPControl 63+4 88±2 5.0+0.4 19+2LBNP (-5 mmnHg) 60±3* 86±2 4.5+0.5* 21+2*Recoverv 62+4 87±2 4.9+0.5 20+2

Effect of handgripControl 60+3 86+2 4.8+0.6 21±210% MIC 62±3* 94+3* 4.9+0.6 22±2Recovery 60±3 89+2 4.9+0.6 21+2Conitrol 62±3 88±2 4.8±0.6 21+220% MIVC 69±4* 99+2* 5.4+0.8 22+2Recoverv 62+3 87+2 5.0+0.6 19+2

Effect of LBNPand handgripControl 59±3 90+2 4.8+0.7 22+2LBNP plus 10% MVIC 60+3 94+2* 4.2±0.6* 26+3*Recovery 60+3 88+2 4.7+0.7 21±2Control 62±3 87±2 4.6+0.6 21+2LBNP plls 20% MNIC 68-+3* 104 +3* 4.5+±0.6 28+4*Recovery 63+3 87±2 4.8±0.6 20+2

Entries represent the mean value+l SEM.* Values that are significantly different from control (P < 0.05).

the vasomnotor center and sympathetic efferent activity.The data further suggest that removal of the inhibitoryinfluence augments the vasoconstrictor response tostimulation of somatic receptors. The slope of theresponise to handgrip at 10 and 20% MVCwas notonly slhifted uip and to the left during LBNP but itbecamiie steeper (Fig. 2). An interaction, mainly l)e-tween an inhibitory cardiopulmoniary reflex andexcitatory somnatic reflex, must take place to producea steeper stimutilus-response cturve and a net responsegreater thani the sUmIl of the two individual reflexresponses at two levels of handgrip (10 anid 20% MVC).

This interpretation of the forearm vascular responsesis dependent on an uinderstanding of the effect ofLBNP on the reflex influence from four groups ofreceptors: soimiatic receptors, cardiopulmonary re-ceptors with vagal afferents, cardiopulmonary recep-tors with symnpathetic afferents, and mesentericreceptors with spinal afferents. Naturally, this under-standing is based on evidence from studies in experi-mental animials. The vagal afferents mediate inhibitoryinfluenices oni syimipatlhetic ouitflow to peripheral beds(13). These receptors are sensitive to changes involume and, thuis, LBNP would reduce the inhibitoryinput fromii these receptors and result in an increasein symipathetic vasomiiotor activity. Cardiopulmonaryreceptors with sympathetic afferents appear to mediate

largely excitatory influences (19). These influencesmay be mediated at spinal and supraspinal levels.It should be noted that reflex effects mediated bythese endings may be difficult to detect when vagalafferents and sinoaortic pathways are intact. It wouldbe anticipated that LBNP would reduce the inputfrom these endings. If cardiopulmonary receptorswith sympathetic afferents exert a tonic excitatoryinfluence on vasomotor outflow to the peripheralcirculation, removal of such an influence would resultin an inhibitory response rather than the excitatoryone that we observed in the forearm during LBNP.Somatic receptors activated during exercise mediategeneralized excitatory responses (20). There is littlereason to suspect an important influence of LBNPon these endings. Mesenteric receptors appear tomediate excitatory influiences during increases invenous pressure which, thus far, have been demon-strated to occur only at the spinal level (21). LBNPwould, however, be expected to excite these endingsand induce excitatory responses.

Thus, LBNPcould augment the response to handgripeither by withdrawing an inhibitory cardiopulmonaryreflex or by augmenting an excitatory mesentericreflex. The role of the mesenteric reflex may be minorfor the following reasons. It has been shown byClement et al. (22), that in the rabbit with sinoaortic

Potentiation of Somatic Reflex Response in Humans 1493

Effect of LBNPF Con~trol

Flow L 4.3 4.2B.P. 120/70Res. 20.5

BNP

4.4 4.31122/70

20.0

Effect of HandgripE- Control

Flow L 4.6 4.9B.P. 122/76Res. 19.2

Effect of LBNP and Handgrip

Flow L 4.0B.P. 120/78Res. 23.3

20% MVC

/1 /~~~~~~~~~~~~~~~~~~4.2 4.3 \i

122/9023.8

20% MVC+ LBNP

'2.5 2.2130/100

46.8

Recovery

4.8 4.7110/76

18.3

Recovery

4.0 3.4120/80

25.1

H-I10 s

FIGURE 1 Plethysmiiographic tracings obtainedl in one slbl)ject befhOre, durinig, an(l after threeinterventionis: (a) LBNPat -5 mmnHg, (b) handgrip at 20% of MVC, anid (c) LBNPaind( handgrip.Calculatedl value of forearm 1)lood flow in milliliters per iuinute per 100 ml of forearmii volumne areshown beneath each tracing. Corresponding values of arterial pressure (B.P., millimeters of Hg)and calcSulated forearm vascular resistance (Res.) are also shown. This figuire shows responsesof a subject in whomthe reflex effects were particularly strikinig.

baroreceptor denervation, expansion of the bloodvolumiie reduces renal nerve activity. After section of'the vagal nerves, no change in renal nerve activity wasobserved during volumile expansion, even though thedischarge of mesenteric receptors would most likelyhave been augml-ented during increases in venouspressture that normally accompany volume expansion.We have observed similar results in the dog (23). Inadditioni, it should be noted that the suction box usedin our studies applies negative pressure at and belowthe level of the iliac crests. Venous pressure in mostmesenteric and other intraabdominal veins would beexpected to decrease during LBNP so that the dis-charge of tonically active excitatory receptors in thisarea would be reduced. On this basis, it is most likelythat the augmentation of the excitatory somatic reflexin the forearm by LBNP is mainly the result of a with-drawal of an inhibitory cardiopulmonary reflex, but wecannot completely exclude the possibility that mesen-teric veins in the pelvis are distended during LBNPand contribute to the excitatory reflex.

In the present study, as well as in previous studies inman (5, 6), LBNP at low levels of suctioin was sufficientto cause reflex forearm vasocon!striction in the absence

of tachyeardia and( signiificant decreases in arterialpressure. Becauise this level of LBNP does not sig-nificantly chanige arterial pressure (5, 6), it seemnsreasonable to suiggest that low level LBNP, like non-hypotensive hemorrhage in animuals, decreases thetonic inhibitory influenice of cardiopulmonary re-ceptors on efferent sympatlhetic activity withoutimportantly altering the stimiiulus to the aiterialbaroreceptors (24, 25).

The marked augmentation of the reflex responseto isometric exercise when the cardiopulmoniaryreceptors were inhibited by LBNP suggests an inter-action l)etween the two reflexes rather than a sunmma-tion of the responses. Several studies have reaffirmedthe concept of interaction of reflexes in the control ofcirculation. Wehave shown such interactions betweenarterial baroreceptors and chemoreceptor reflexes(26), between cardiopulm-onary receptor and arterialbaroreceptor as well as chemoreceptor reflexes (27, 28),and between somatic and arterial as well as cardio-pulmonary reflexes in animals (16, 17). This is thefirst demonstration that an excitatory reflex in man isaugmented by removing the tonic inhibitory influenceof the cardiopulmonary receptors.

1494 J. L. Walker, F. M. Abboud, A. L. Mark, and M. D. Thamnes

Recovery

4.7 4.6120/70

18.7

A Mean Arterial Pressure .

IH.G. H.G.10% 20%MVC MVC

LBNP LBNP+ +

H.G. H.G.10% 20%

A Forearm Blood Flow

A ForearmVascular Resistance

T'F'LBNP H.G. H.G.

-5 mmHg 10% 20%MVC MVC

*

LBNPH.G.10%

I A Heart RateI6 -

cncv)4

21-

LBNPH.G.20%

-2

LBNP-5 mmHg

EIH.G. H.G.10% 20%MVC MVC

FIGURE 2 Changes in meani arterial pressuire, forearm)0blood flow, forearmii vascular resistanice,and heart rate that resulte(d fromn LBNPat -5 mmnHg, from isometric handclgril) (H.G.) at 10 and 20%of MVC, and during concomnitanit LBNP and H.G. at 10 and 20% of MVC. The chalnlges in eachsulbject were caleculated by subtracting the value obtained durinig the intervenition from thecontrol value. Asterisk (*) indicates that response to LBNPplts H.G. at 10% MVCis significantlygreater (P < 0.05) than the algebraic stum of LBNP alone pltis H.G. at 10% M1VCatlone. Doubleasterisk (**) inidicates that responise to LBNPplts H.G. at 20% MIVC is significantly greater thanthe algebraic stim of LBNPalonie pluis H.G. at 20% M1VCalonie. Changes thalt atre nlot signiificanitlydifferent are so indicated. Data presented as mean-t-SE.

The absence of a significant increase in calculatedforearmn vascular resistance during handgrip alonie dloesnot mnean that there was no increase in vasomnotor toneof forearm resistance vessels. The rise in arterialpressure during exercise was significant, and vaso-motor tone had to increase for vascular caliber to bemainitained and for calcuilated resistance not to de-crease passively. Thus, there was a vasocoInstrictorresponise that was not apparent fromii the calculatedresistance changes. The association of an increasein resistanice in the f:ace of a signiificaint autgmiienitationof' the arterial pressture response, as was seeni durinigcon-comiiitant exercise and LBNP, incdicates that a majorpotenitiation of' this increase in vasomiiotor tonie hadtakeni place.

Despite an increase in arterial pressutre, which wouldbe expected to inhibit sympathetic activity by activat-

ing arterial baroreceptors, the actixationl of' somiuaticreceptors by exercise causes reflex increatses in heartrate anid in vasomotor tone. The most likely explancationifor the sutstaine(l excitatorv response is the reportedinhibition of the arterial baroreceptor reflex duringexercise (11, 29). Althouglh the arterial baroreflex issuppressed durinig exercise, the input fromii the baro-receptors can modulate the siomatic reflex. Work byKumiada et al. (15), as well as previous work from ouirlaboratory (16, 17), lhas showni that, in the dog, thereflex vasocon striction prodtuced bN electrical stimuIail-tion of the central enid of the cutt sciatic nierve is autig-miented by lowerinig carotidl sinuts pressture and re(duicedcwhen carotid sinuis pressture is elevated. The inereasein arterial pressture during exercise couild thuis beexpected to buf'fer the excitattory somaltic reflex but niotprevent it. The imiarked potentiatioin of' the vaso-

Potetl tiatiofl of Sonfi tic Reflex Resp)( 1nse inl Htfl i ai s

141F

12FI)

8F

41LBNP

-5 mmHg0

8r

1-

8 6.l

E- 4:?2

EE

0 ni

N S

N S

LBNP LBNP+ +

H.G. H.G.10% 20%

8 r

1495

constrictor response to exercise during LBNP whichwe observed might have been greater if the simultane-ous rise in arterial pressure had been prevented.

The complexity of the neural control of the circula-tion is evident from the fact that we observed a smallbut significant bradycardia at a time when there wasforearm vasoconstriction. This finding may be bestexplained by a withdrawal of an excitatory reflexduring LBNP. In this regard, it is known that activationof atrial receptors with vagal afferents by volumeloading or by distention of pulmonary vein left-atrialjunctions can result in tachycardia at a time whenvasomotor outflow to the periphery is decreasing (30).This is thought to be the basis for the Bainbridgereflex (30). More recent evidence suggests that cardiacreceptors with sympathetic afferents could alsocontribute to this reflex (24). It can be suggested thatreduced input from atrial receptors with vagal afferentsor from cardiac receptors with sympathetic afferentsduring LBNP was responsible for the small brady-cardia that we observed.

On the basis of our results, a mechanism for thesignificant increase in sympathoadrenal response toexercise noted in humans and animals with heartfailure (31, 32) can be suggested. There is evidencein animals that the sensitivity of atrial receptors withvagal afferents (33, 34) is reduced in congestive heartfailure. Kivowitz et al. (12) has demonstrated a 5-10%increase in systemic vascular resistance with 15%handgrip in patients with coronary artery disease ormild heart failure (class I and II). In patients withclass III heart failure, the increase in systemic vascularresistance with the same level of handgrip was >30%.Several investigators have shown that the sympatho-adrenal response to exercise is increased in patientswith heart failure (35-37). We speculate that thealtered sensitivity and, thus, reduced inhibitoryinfluence of cardiopulmonary receptors in heartfailure may contribute to this increased sympatho-adrenal response to exercise in patients with heartfailure. The observation that reducing the influenceof cardiopulmonary receptors in man leads to anaugmentation of the vasoconstrictor response to iso-metric exercise is consistent with this view. Studiesinvestigating cardiopulmonary receptor function inpatients with heart failure should advance our under-standing of the importance of these receptors andtheir interactions with other reflexes in the heartfailure syndrome.

ACKNOWLEDGMENTS

The authors wish to thank Jinx Tracy for her expert technicalassistance and Nancy Stamp for typing the manuscript.

This research was supported by a Program Project Grant,HL14338, and the Institutional Cardiovascular TrainingGrant HL07121 from the National Heart, Lung and BloodInstitute.

REFERENCES

1. Jarisch, A., and Y. Zotterman. 1948. Depressor reflexesfrom the heart. Acta Physiol. Scantd. 16: 31-51.

2. Mark, A. L., F. M. Abboud, P. G. Schmid, and D. D.Heistad. 1973. Reflex vascular responses to left ventriciu-lar outflow obstruction and activation of ventrictularbaroreceptors in dogs. J. Clin. Intcest. 52: 1147-1153.

3. Oberg, B., and P. Thoren. 1973. Circulatory responsesto stimulation of left ventrictular receptors in the cat.Acta Physiol. Scand. 88: 8-22.

4. Walker, J. L., M. D. Thames, F. MI. Abboud, A. L. Mark,and H. S. Klopfenstein. 1978. Preferential distributionof inhibitory cardiac receptors in left ventricle of'the dog.Am. J. Physiol. 235(2): H188- H192.

5. Zoller, R. P., A. L. Mark, F. M. Abboud, P. G. Schmnid, andD. D. Heistad. 1972. The role of'low pres.sure barorecep-tors in reflex vasoconstrictor responses in mnan. J. ClitG.Invest. 51: 2967-2972.

6. Johnson, J. Ml., L. B. Rowell, M. Niederberger, andM. M. Eisman. 1974. Human splauichnic and forearmvasoconstrictor responses to reduictions of' right atrialand aortic pressures. Circ. Res. 34: 515-524.

7. Lind, A. R., S. H. Taylor, P. W. Huimphreys, B. MI.Kennelly, and K. W. Donald. 1964. The circtulatoryeffects of sustained voluntarv mutscle contractioni. CliGl.Sci. Mol. Med. 27: 229-244.

8. Bevegard, B. S., and J. T. Shepherd. 1966. Reaction inman of resistanice and capacity vessels in forearm andhand to leg exercise.J. Appl. Phiysiol. 21: 123-132.

9. McCloskey, D. I., and J. H. Mitchell. 1972. Reflexcardiovascular and respiratory responses originating inexercising mtuscle. J. Physiol. (Lond.). 224: 173-186.

10. Freyschuss, U. 1970. Cardiovascullar effects of voluntaryisometric mulscle contractions. Acta Physiol. Scanid.Suppl. 342: 12-19.

11. Bristow, J. D., E. B. Brown, D. J. C. Ctnniinighamii, NM. G.Hanson, E. S. Petersen, T. G. Pickering, anld P. Sleight.1971. Effect of bicycling on the baroreflex reguilationof pulse interval. Circ. Res. 28: 582-592.

12. Kivowitz, D., W. W. Parmley, R. Donoso, H. NMarcus,W. Ganz, andl H. J. C. Swan. 1971. Effects of' isomiietricexercise on cardiac performance. The grip test. Circtla-tion. 44: 994-1002.

13. Thor6n, P. N., D. E. Donald, anid J. T. Shepherd. 1976.Role of heart and lung receptors with nonmlledtullatedvagal afferents in circulatory control. Circ. Res. 28:11-2-9.

14. Fox, I. J., D. A. Gerasch, and J. J. Leonard. 1977. Leftventricular mechanoreceptors: a hemiiodlyniamic study.J. Physiol. (Lond.). 273: 405-425.

15. Kumada, M., K. Nogami, and K. Sagawa. 1975. Modulationof carotid sinus baroreceptor reflex by sciatic nervestimulation. Amit. J. Physiol. 228: 1535-1541.

16. Mark, A. L., H. Koike, anid F. M. Abboud, 1975. Inhibitionof the somatic pressor reflex by increases in carotidbaroreceptor activity. Clin. Res. 23: 473A.

17. Thames, M. D., and F. M. Abboud. 1979. Interaction ofsomatic receptors with cardiopulmoniary and carotidbaroreceptors in the control of the renal circulationi indogs. Am. J. Physiol. 6: H560- H565.

18. Whitney, R. J. 1953. The measuremiient of volume chiailgesin human lim-bs.J. Physiol. (Lon(l.). 121: 1-27.

19. Malliani, A. 1979. Afferent cardiovasctular sympattlheticnerve fibers anid their function in the neuiral regulationi ofthe circulationi. In Cardiac Receptors. R. Hainswvorth,C. Kidd, an(d R. J. Linden, editors. Camnlbridge UniversityPress, Cambridge, England.

20. Tibes, U. 1977. Reflex inputsi to the calrdiovasctular and(c

1496 J. L. Walker, F. M. Abboud, A. L. Mark, and M. D. Thames

respiratory centers from dynamically working caninemuscles. Some evidence for involvement of group III orIN' nerve fibers. Circ. Res. 41: 332-341.

21. Anclrews, C. J. H., XV. H. H. Acllerews, and J. Orbach. 1972.A sympathetic reflex elicited by distenision of themeseniteric venous bed.J. Phtysiol. (Loutd.). 226: 119-131.

22. Clemiienit, D. L., C. L. Pelletier, and J. T. Shepherd. 1972.Role of vagal afferenits in the conitrol of rencal syn-ipatheticnerve activity in the rabbit. Circ. Res. 31: 824-830.

23. Tlhamiies, NI. I)., F. MI. Abboud, L. A. WVaickman, andR. P. Richter. 1980. Reflex stuppression of renal nerve ac-tivitv by cardiac receptors with vagal afferents: sensitizal-tion by acetylstrophanthidin. Clin. Res. 28: 215A. (Abstr.)

24. Guipta, P. D., and NI. Singh. 1977. Autoniomiiic afferenltsat T, ini elicitation of' volume-induced tachycardcia inthe clog. Am J. Philsiol. 232: H464-469.

25. Thamiies, NI. D., NI. Jarecki, ancd D. E. Donald. 1978.Neuiral conitrol of reniin secretioin in aniesthetized clogs.Interactioni of cardioptulmonary ancd carotid baroreceptors.Circ. Res. 42: 237-245.

26. Heistacl, D. D., F. MI. Abboucl, A. L. NMark, and P. G.Sclhmiii(l. 1974. Interactioni of' baroreceptors and chemo-receptor reflexes. J. Cliii. In vest. 53: 1226-1236.

27. Koike, H., A. L. Mlark, D. D. Heistad, and(c P. G. Schmicl.1975. Inifluienice of cardioptulmonary vagal afferenit activityo01 catrotid chemoreceptor aindl baroreceptor reflexes in thedog. Circ. Res. 37: 422-429.

28. Takeslhita, A., A. L. MNark, D. L. Eckberg, and F. NI.Abboucl. 1979. Effect of cenitral venouis pressture onarteriall baroreflex cointrol off heart rate. Am. J. Phlysiol.236(1): H42-1H47.

29. Pickerinig, T. G., B. Gribbin, E. S. Petersen, D. J. C.

Cunninghaimi, and P. Sleight. 1972. Effects of autonomicblockade on the baroreflex in mnan at rest and duiringexercise. Circ. Res. 30: 177-185.

30. Lindleni, R. J. 1975. Reflexes from the heart. Prog. Cardio-awsc. Dis. 18: 201-221.

31. Higgins, C. B., S. F. Vatner, D. Franklin, and E. Braun-wald. 1972. Eff'ects of' experimentallx produced heartf:ailure oIn the peripheral vascular responise to severeexercise in conisciouts dogs. Circ. Res. 31: 186-194.

32. Wood, J. E., J. Litter, and R. W. Wilkins. 1956. Peripheralvenoconstriction in humian congestive heart failure.Circtulationt. 13: 524-527.

33. Greenberg, T. T., W. H. Richmond, R. A. Stockling,P. D. Gupta, J. P. Mleehan, and J. P. Henr. 1973. Impairedatrial receptor responses in (logs with heart failure clue totricuispid insuifficiency and pulmonary artery steniosis.Circ. Res. 32: 424-433.

34. Zucker, I. H., A. NI. Earle, and J. P. Gilmore. 1977. Themechanismiis of' adaptation of' left atrial stretch receptorsin clogs with chronic congestive heart failure. J. Clin.Invest. 60: 323-331.

35. Wood, J. E. 1962. The mechacnism of'the increased venouspressure with exercise in conigestive heart failure. J.Cliti. Invest. 41: 2020-2024.

36. Chiclsev, C. A., D. C. Harrison, anid E. Brauniwalid. 1962.Auigmentation of the plasmiia norepinephrine responiseto exercise in patients with congestive heart f:ailure. N.Engl. J. Med. 267: 650-654.

37. NMillard, R. XV., C. B. Higgins, D. Franklin, and S. Vattner.1972. Regulationi of the renal circulation dturing severeexercise in normiial dogs and dogs with experimenitalheart failure. Circ. Res. 31: 881-888.

Potentiation of Somiiatic Reflex Response in Humnans 1497