Reflex Vascular Responses to Left

Ventricular Outflow Obstruction and Activation of

Ventricular Baroreceptors in Dogs

ALLYN L. MARK, FRANCOISM. ABBOUD,PHILLIP G. SCHMID,and DONALDD. HEISTAD with the technical assistance ofU. JAMESJOHANNSEN

From the Cardiovascular Division, Department of Internal Medicine,University of Iowa College of Medicine and the Veterans AdministrationHospital, Iowa City, Iowa 52240

A B S T R A C T Reflex vascular responses to acute leftventricular outflow obstruction were studied in anes-thetized dogs. The studies were done to compare theeffects of activation of ventricular baroreceptors onvascular resistance in skeletal muscle (gracilis muscle)and skin (hindpaw); to identify afferent and efferentpathways which mediate the reflex vasodilatation; andto assess the relative contribution of ventricular baro-receptors and baroreceptors in left atrium and pul-monary vessels in responses to left ventricular outflowobstruction. The gracilis artery and the cranial tibialartery to the paw were perfused separately at constantflow. Changes in perfusion pressure to each bed re-flected changes in vascular resistance. Outflow obstruc-tion was produced by inflating a balloon in the leftventricular outflow tract for 15 s while pressures in theleft ventricle and aortic arch were measured.

Inflation of the balloon increased left ventricularpressure and decreased pressure in the aortic arch. Lowand high levels of obstruction produced dilator re-sponses averaging -543 (SE) and -42411 mmHgin muscle and -14-1 and -3±i2 mmHg in paw.Denervation, phentolamine, and glyceryltrinitratecaused greater dilatation in paw than did left ventricularoutflow obstruction. This indicates that dilator re-sponses in the paw were not limited by a low level ofresting neurogenic constrictor tone or by a negligibledilator capacity of these vessels.

This work was presented in part at the 44th Annual Sci-entific Sessions of the American Heart Association, Ana-heim, California, 12 November 1971.

A preliminary report has appeared in abstract form, Cir-culation. 43: II-76.

Received for publication 2 Novemiber 1972 and in revisedformn 15 January 197 3.

Obstruction to left ventricular inflow increased leftatrial pressure, but did not cause reflex vasodilatation.This suggests that low pressure baroreceptors in atriaor pulmonary vessels did not contribute to vasodilatorresponses to left ventricular outflow obstruction.

Vasodilator responses to outflow obstruction wereblocked by bilateral vagotomy, sectioning the sciaticand obturator nerves, and administration of phento-lamine, but were not decreased by atropine ortripelennamine.

The results indicate that activation of left ventricularbaroreceptors produces striking vasodilatation in skeletalmuscle, but only slight vasodilatation in skin. The datasuggest that the difference in dilator responses in thetwo beds results from greater withdrawal of adrenergicconstrictor tone to skeletal muscle than to skin. Activa-tion of sympathetic cholinergic or histaminergic dilatorpathways does not contribute to the dilatation.

INTRODUCTION

Left ventricular distention in dogs produces reflexhvpotension and vasodilatation (1-3).

In the preceding study, we demonstrated that reflexforearm vasoconstrictor responses to leg exercise arereversed in patients with aortic stenosis and a historyof syncope. Wesuggested that this reversal results fromincreases in left ventricular stretch and activation ofventricular baroreceptors (4).

The present experiments in dogs were done to explorefurther the mechanism by which left ventricular outflowobstruction might promote vasodilatation.

We assessed the relative contribution of ventricularbaroreceptors and of low pressure baroreceptors in atria

The Journal of Clinical Investigation Volume 52 May 1973 *1147-1153 1147

and pulmonary vessels to the reflex vasodilator responseto left ventricular outflow obstruction. These experi-ments were done because left atrial pressure, as well asleft ventricular pressure, increases during outflowobstruction.

Since some reflex stimuli produce different effects onvessels in skin and skeletal muscle (5-6),we comparedeffects of left ventricular outflow obstruction on vascu-lar resistance in the gracilis muscle and in the hindpaw,which has a predominantly cutaneous vascular bed.

Studies also were performed to identify the efferentcomponents of the sympathetic nervous system whichare involved in reflex vasodilaattion during left ventric-ular outflow obstruction. Wewanted to determine if thevasodilatation results from withdrawal of adrenergicconstrictor tone or from activation of sympatheticcholinergic or histaminergic dilator pathways (7-9).

Specifically, the experiments were designed: (a) tocompare effects of left ventricular outflow obstructionon vascular resistance in skeletal muscle and skin,(b) to define the mechanism for differences in responsesin the two beds, (c) to assess the relative role of ven-tricular baroreceptors and of left atrial or pulmonaryvascular baroreceptors in responses to left ventricularoutflow obstruction, (d) to identify afferent and efferentpathways, particularly the efferent component of thesympathetic nervous system which is involved in thedilatation, and (e) to determine if an intact carotid sinusreflex attenuates the dilator responses to left ventricularoutflow obstruction and activation of ventricularbaroreceptors.

METHODS

Male mongrel dogs weighing 22-29 kg were anesthe-tized with chloralose, 50 mg/kg, and urethane, 500mg/kg, treated with decamethonium bromide, 0.3mg/kg, intravenous (i.v.), and ventilated artificially.

The cranial tibial artery to the hindpaw was exposednear the tarsus, and collateral arteries at this level wereligated. The gracilis muscle in the same limb was dis-sected free from surrounding tissues with the exceptionof the gracilis artery, vein, and nerve. The cranialtibial and gracilis arteries were cannulated and perfusedseparately at constant flow with heparinized arterialblood from a femoral artery and a small reservoir whileperfusion pressures were recorded. Flows ranged from18-22 ml/min to the hindpaw and 8-12 ml/min to themuscle; these flows produced perfusion pressures in thesame range as arterial pressure at the start of the study.With flow constant, changes in perfusion pressure toeach bed indicated changes in vascular resistance. Per-fusion pressures abruptly fell to 10-20 mmHg when thepumps were stopped, and there was little or no backflow of blood from the distal end of the partially tran-sected vessels suggesting that there was little or no

collateral flow. Perfusion pressures did not fall when theinflow tubing to the reservoir was clamped for 90 s. Thisobservation indicates that during the interventionsflows and perfusion pressures were independent ofchanges in arterial pressure.

A rigid double lumen balloon cannula was insertedinto the left carotid artery and advanced so that thetip was in the outflow tract of the left ventricle. Pres-sure at the tip of this cannula was measured. A balloonlocated 5 mmfrom the tip of the cannula was inflatedwith 5-20 ml of air to produce left ventricular outflowobstruction. Arterial pressure was measured with acatheter in the aortic arch. The position of the catheterin the aortic arch was determined either by palpatingthe tip through a thoractomy or by inserting the tipinto the left ventricle and withdrawing the catheter1-2 cm beyond the point where the pressure contourchanged from vnetricular to arterial. Inflation of theballoon increased left ventricular pressure and decreasedin the aortic arch.

Wemeasured responses to two levels of left ventricu-lar outflow obstruction in muscle and paw in six dogs.The low level of obstruction was produced by rapidlyinflating the balloon with 7.5-10.0 ml of air for 15 s.The high level was produced by inflating with 15.0-20.0 ml.

In 11 experiments, we compared dilator responses inpaw during ventricular outflow obstruction with dilatorresponses caused by denervation (n = 5), phentolamine(2.5 mg intraarterial (i.a.); n = 4) and glyceryltrini-trate (6 ,g i.a.; n = 10). These comparisons were madeto determine if dilatation in the paw during outflow ob-struction was limited either by a low level of adrenergicconstrictor tone or by the dilator capacity of vessels inthe paw.

The relative contribution of left ventricular baro-receptors and low pressure baroreceptors in the leftatrium or pulmonary vessels was studied in four ex-periments by comparing responses to left ventricularoutflow and inflow obstruction. Inflow obstruction wasproduced by inserting a flexible balloon catheter intothe left atrium and inflating the balloon at the mitralvalve to increase left atrial pressure. Decreases inarterial pressure, which promote reflex vasoconstrictionby activating carotid sinus reflexes, were greater duringoutflow than inflow obstruction. In order to minimizeeffects of the difference in the arterial pressure responseon the comparison of the vascular responses to outflowand inflow obstruction, the carotid sinuses were dener-vated before these interventions.

Responses to outflow obstruction were obtainedbefore and after bilateral cervical vagotomy in threeexperiments, and before and after cutting the obturatorand sciatic nerves to muscle and paw, respectively, inthree experiments. These experiments were done to

1148 A. Mark, F. Abboud, P. Schmid, and D. Heistad

demonstrate that the responses were neurogenicallymediated and to identify afferent and efferent pathways.

We then performed experiments to identify the effer-ent component of the sympathetic nervous systemwhich mediated the vasodilatation. In four studies re-sponses to outflow obstruction were obtained beforeand after administration of the alpha receptor blockingagent, phentolamine (2.5 mg i.a.), which was given torelease adrenergic constrictor tone. Phenylephrine(4 lig i.a.) was injected to test effectiveness of blockadeby phentolamine. The rationale of the experimentswith phentolamine was that if the dilator response tooutflow obstruction results from withdrawal of adrener-gic constrictor tone, then release of resting adrenergicconstrictor tone with phentolamine would prevent thedilatation. As a result of previous experiments with phen-tolamine, we anticipated a problem in the interpreta-tion of these experiments since phentolamine not onlyreduces dilator responses which result from withdrawalof adrenergic constrictor tone, but also reduces re-sponsiveness to other dilator stimuli (for example,glyceryltrinitrate) by decreasing resting vascular re-sistance. This raised the possibility that phentolaminemight block the dilator responses to outflow obstructionspecifically by preventing withdrawal of adrenergicconstrictor tone or nonspecifically by reducing thedilator capacity of these vessels. In order to determineif phentolamine was blocking the dilatation specificallyby preventing withdrawal of adrenergic constrictortone, we used the ratio of the dilator response to outflowobstruction divided by the dilator response to the non-specific vasodilator, glyceryltrinitrate. A decrease inthe ratio after phentolamine would indicate a specificblockade of the dilatation during outflow obstruction.Responses also were measured before and after ad-ministration of atropine (1.0 mg i.v.) and tripelen-namine (5.0 mg i-v.), which were given to determine ifthe dilatation resulted from activation of sympatheticcholinergic or histaminergic dilator pathways. Efficacyand specificity of blockade with these agents weretested with injections of acetylcholine (16 jig i.a.),histamine (2 jig i.a.), and glyceryltrinitrate (6 jigi.a.).

In four additional experiments, we obtained responsesto outflow obstruction and to carotid occlusion beforeand after cutting the carotid sinus nerves. These ex-periments were done to see if abolishing the carotidsinus reflex augments dilator responses to outflow ob-struction by preventing reflex vasoconstrictor responsesto decreases in arterial pressure.

Statistical comparisons were performed with the ttest for paired data (10). Statistical significance wasindicated by P values <0.05. The one-tailed t test wasused to analyze effects of vagotomy, denervation, andblocking drugs on vasodilator responses.

+ILow level

High levelmean ± SEn = 6

E +40 -

E

C,,

0n

- 40-

- 80 -

LVP SAP PAW MUSCLE

FI(URE 1 Responses to two levels of left ventricular outflowobstruction. LVP, left ventricular pressure, SAP, systemicarterial pressure measured in the aortic arch; PAW, perfusionpressure to hindpaw; and MUSCLE, perfusion pressure togracilis muscle.

RESULTS

Responses to graded left ventricular outflow obstruction.Inflation of the balloon in the left ventricular outflowtract increased (P < 0.05) left ventricular pressure anddecreased (P < 0.05) pressure in the aortic arch(Figs. 1 and 2). Increases in left ventricular pressurewere associated with pronounced vasodilatation inmuscle and slight, insignificant vasodilatation in paw(Fig. 1).

Vasodilator responses to outflow obstruction in thepaw were compared with vasodilator responses to dener-vation, phentolamine, and glyceryltrinitrate in anothergroup of experiments. In these experiments, decreasesin perfusion pressure in paw with outflow obstructionaveraged -11±3 (SE) mmHg and were significantlyless (P < 0.05) than decreases with denervation(-464±10 mmHg), phentolamine (-704±25 mmHg),and glyceryltrinitrate (-3346 mmHg).

Comparison of vascular responses to left ventricularoutflow and inflow obstruction. Outflow obstruction in-creased (P < 0.05) left ventricular and left atrial pres-sures and produced significant vasodilatation (Figs. 2and 3). In contrast, inflow obstruction, which resultedin increases in left atrial pressure comparable to thosewith outflow obstruction, failed to produce vasodilata-tion (Figs. 2 and 3).

Reflex Vascular Responses to Left Ventricular Outflow Obstruction 1149

LV l O

FIGURE 2 Comparison of left ventricular outflow (LVOO)and inflow (LVIO) obstruction.

Effects of vagotomy and denervation. Vasodilator re-

sponses in paw and muscle were blocked (P < 0.05)by vagotomy or by cutting the sciatic and obturator

Outflow obstruction

+80 Inflow obstruction

mean SE

n 4

Carotid sinuses denervated

+40 _E

00

-40-

-80LLVP SAP LAP PAW MUSCLE

FiGURF, 3 Responses to left ventricular outflow and inflow

obstruction.

Inflow Obstruction

... ....

.. .. ..* A. . . ; . . S S .Promo____...... .. . . .. X . . . . . i:. ..

hi___-

... ... ... ... ..

C'

I

EE

w

(I)

0.

z

0

w

CL

Vagotomy

PAW MUSCLE

BeforeAfter

mean ±SEDenervation

PAW MUSCLE

FIGURE 4 Effects of bilateral cervical vagotomy and ofdenervation of paw and muscle on vascular responses to leftventricular outflow obstruction.

nerves (Fig. 4). Increases in left ventricular pressure

during outflow obstruction were similar (P > 0.05)before and after these interventions.

Effects of blocking agents. Phentolamine blocked(P < 0.05) dilator responses to outflow obstruction inpaw and muscle (Fig. 5). This dose of phentolaminereduced vasoconstrictor responses to the alpha receptor

stimulating agent, phenylephrine, from 103433(mean ±SE) mmHg to 2±2 mmHg in paw (P < 0.05)and 17±4 to 2±:2 mm Hg in muscle (P < 0.05).Phentolamine also reduced responses to glyceryltrini-trate, which was used as an internal dilator control,from -40±7 to -7±2 mmHg in paw and -38±7 to-18±4 mmHg in muscle (P < 0.05). This indicatedthat phentolamine reduced the dilator capacity ofvessels in paw and muscle. In order to determine if theblockade of dilator responses to outflow obstructionwith phentolamine resulted from specific or nonspecificeffects, we used the ratio of dilator responses to outflowobstruction divided by dilator responses to an internaldilator control, glyceryltrinitrate. In three studies inmuscle, the ratio was 3.40, 0.88, and 1.40 before phen-tolamine and 0.00, 0.25, and 0.20 after phentolamine,respectively. The decrease in the ratio after phentola-mine indicates that the drug produced specific blockadeof the dilator responses to outflow obstruction in addi-tion to a reduction in the dilator capacity.

Atropine blocked (P < 0.05) dilator responses to

acetylcholine, but did not decrease (P > 0.05) re-

sponses to outflow obstruction (Figs. 5 and 6). Re-

sponses to acetylcholine in paw and muscle averaged-28±3 and -41±9 mmHg before and -1±1 and-1±1 mmHg after atropine (P < 0.05). Administra-tion of atropine did not alter dilator responses to

1150 A. Mark, F. Abboud, P. Schmid, and D. Heistad

Outflow Obstruction

200

SAP L(mm Hg)

200:

(mm Hg)

200.MUSCLE~~~~~~~~~~.PP. ...s... ;.

5 0

(mm Hg)

20... S.....

PAW PP( m g ...

LJ

(mm Mg)_

LVOO15 s

Phentolamine

c::: Before* After

mean ± SEAtropine Tripelennamine

,} zz.;a l.A. }(A1.0mg IV. ) (5.0mg I.V.)D n=4 n=5 n=3

W PTAW MSLPA MUCEPWMSE

Cl)

z E -3002EU.

"W -60-a. ~PAW MUSCLE PAW MUSCLE PAW MUSCLE

FIGURE 5 Effects of phentolamine, atropine and tripelennamine on responses to left ventricularoutflow obstruction.

glycerltrinitrate; responses to glyceryltrinitrate in pawand muscle averaged -28±3 and -45±2 mmHg, re-spectively, before atropine and -24±2 and -36±-8mmHg after atropine (P > 0.05). Tripelennamine re-duced dilator responses to histamine, but did not reduce(P > 0.05) dilator responses to outflow obstruction.Responses to histamine in paw and muscle averaged-10±3 and -24±;9 mm Hg, respectively, beforetripelemennamine and -2±-2 and -3±2 mmHg aftertripelennamine (P < 0.05). Dilator responses to gly-ceryltrinitrate in paw and muscle were not reduced andaveraged -18±-6 and -27±-7-27±4 and -43±t4 mmHg(P > 0.05).

Before Atropine200 -

SAP(mm Hg)

I

LVP 4OO[i-j L(mm Hg) L

200 _

PAW PP J

(mm Hg)

200 1-

MUSCLE PP L =(mm Hg) IJ

LVOOI5sS

mmHg before andafter tripelennamine

Af ter Atropine

1 I'---... ---- t--t--- t t-- -

LVOO

FIGURE 6 Responses to left ventricular outflow obstruction(LVOO) before and after atropine. The delay in the onset ofthe reflex vasodilator response in the muscle compared to skinwas not a consistent finding.

Effects of carotid sinus denervation. Sectioning thecarotid sinus nerves reduced (P < 0.05) vasoconstrictorand vasopressor responses to carotid occulsion (Fig. 7)and tended to augment vasodilator responses to out-flow obstruction in muscle, but not in paw (Fig. 7).The vasodilator responses in the muscle were greaterafter carotid sinus denervation in each of the four dogs,and averaged -25+9 mmHg before and -56±22mmHg after carotid sinus denervation (P > 0.05).Increases in left ventricular pressure with outflow ob-struction were less after denervation averaging 109±414before and 90±12 mmHg after denervation (Fig. 7).

DISCUSSION

These studies indicate that reflex vasodilatation in theextremities caused by left ventricular outflow obstruc-

Left Ventricular Outflow Obstruction+ 1 20

(top)andcarotidocclusion t Beforeftre+80ocaro After

_.... mean SE+40 n=4

E :::GE ..

l-02

Carot id Occ lusion

LVP SAP PAW MUSCLE

FIGURE. 7 Responses of left ventricular outflow obstruction(top) and carotid occlusion (bottom) before and after denerva-tion of carotid sinus.

Reflex Vascular Responses to Left Ventricular Outflow) Obstruction 1151

tion and activation of ventricular baroreceptors occurspredominately in skeletal muscle. Vasodilatation in thepaw, which has a predominately cutaneous vascularbed, is minimal. Weconsidered the possibility that thedilator response in the paw was limited either by a lowlevel of resting neurogenic constrictor tone of cutaneousvessels or by a negligible dilator capacity of thesevessels. These possibilities seem unlikely since denerva-tion to release neurogenic tone, phentolamine to releaseadrenergic constrictor tone, and glyceryltrinitrate totest the dilator capacity of these vessels, all produceddilator responses which were greater than responses toleft ventricular outflow obstruction. The earlier ob-servation that another reflex stimulus, activation ofarterial chemoreceptors, produces reflex vasodilatationin the paw (5) provides additional evidence that thedilator response in the paw was not limited by failureof these vessels to dilate in response to neurogenicstimuli. These observations suggest that the differencein the magnitude of the dilator response in muscle andskin during activation of ventricular baroreceptors mayresult from greater withdrawal of sympathetic nervetraffic to skeletal muscle. This appears to occur alsowith activation of carotid sinus baroreceptors sincecarotid sinus nerve stimulation causes greater dilatationin muscle than skin (11). The peak vasodilator responseoccurred later in muscle than in paw. It is difficult todraw conclusions about the relative timing of the reflexresponse to outflow obstruction in the two beds fromthis observation since the magnitude of the responsewas less in paw than in muscle. The peak reflex vaso-constrictor response to carotid occlusion also occurredlater in muscle than in paw in these studies, but thisresponse was also greater in muscle.

It is difficult from these experiments to identify thethreshold for the increases in left ventricular pressurewhich are required to produce reflex vasodilatation.Since the carotid sinuses were intact in most of theseexperiments, the change in vascular resistance duringoutflow obstruction represents the net effect of vaso-dilatation resulting from increases in left ventricularpressure and vasoconstriction resulting from decreasesin systemic arterial pressure. Therefore, attempts to

determine the magnitude of increases in left ventricularpressure which are required to cause reflex vasodilata-tion from this study would probably overestimate thethreshold. Striking vasodilatation usually occurred onlyduring increases in left ventricular pressure of more than50 mmHg, but definite vasodilatation was seen in fourexperiments with increases of left ventricular pressureof 15-40 mmHg despite a fall in arterial pressure whichwould be expected to produce reflex vasoconstriction.

In the preceding study, we demonstrated that fore-arm vasoconstrictor responses to leg exercise are in-

hibited or reversed in patients with aortic stenosis (4)and suggested that this results from activation of ven-tricular baroreceptors. Since reflex forearm vasocon-striction during leg exercise occurs largely in skeletalmuscle (12), the results of the present study are con-sistent with the suggestion that reflexes arising in ven-tricular baroreceptors could inhibit or reverse theconstriction.

Baroreceptors in atria and pulmonary vessels par-ticipate in the regulation of vascular tone (13-14).Since left atrial pressure increased during left ventricu-lar outflow obstruction, we had to evaluate the con-tribution of reflexes arising in atrial or pulmonaryvascular baroreceptors. Inflation of a balloon at themitral valve produced increases in left atrial pressurewhich were comparable to those resulting from outflowobstruction, but failed to produce vasodilatation.Decreases in arterial pressure, which promote reflexvasoconstriction by activating carotid sinus reflexes,were greater during outflow than inflow obstruction.The effect of this difference in arterial pressure responseon comparisons of vascular responses to outflow andinflow obstruction was minimized by denervating thecarotid sinuses before the interventions. In addition, itshould be noted that even with intact carotid sinus re-flexes, the greater decreases in arterial pressure duringoutflow obstruction would promote vasoconstrictionand reduce, not augment, the vasodilator response.Therefore, the greater vasodilator responses duringoutflow obstruction cannot be explained by the changesin arterial pressure. The results of these experimentssuggest that reflex vasodilatation during left ventricularoutflow obstruction resulted from activation of leftventricular baroreceptors and not from low pressurebaroreceptors in atria or pulmonary vessels. Theseresults are consistent with the finding in the precedingstudy that forearm vasoconstrictor responses to legexercise are inhibited in patients with aortic stenosis,but not in patients with mitral stenosis (4).

Responses to left ventricular distension cannot beattributed to myocardial ischemia since coronary arteryocclusion produces reflex vasodilatation in paw andvasoconstriction in muscle (6) in contrast to slightdilatation in paw and pronounced dilatation in musclein this study.

Aviado and Schmidt (1) demonstrated that reflexvasodilator responses to left ventricular stretch are

mediated through vagal afferent and sympatheticefferent pathways. Reflex vasodilatation produced bystimulation of carotid sinus baroreceptors results fromboth withdrawal of adrenergic constrictor tone andactivation of sympathetic dilator pathWays (15-16).Our study suggests that reflex vasodilatation caused byactivation of ventricular baroreceptors results from

1152 A. Mark, F. Abboud, P. Schmid, and D. Heistad

withdrawal of adrenergic constrictor tone. Phentola-mine, which releases adrenergic tone by blocking alphareceptors, abolished the dilatation during outflow ob-struction, but also resulted in a nonspecific reductionin dilator capacity by decreasing resting vascular re-sistance. Phentolamine decreased the ratio of dilatorresponses to outflow obstruction divided by responsesto an internal dilator control, glyceryltrinitrate. Inother words, blockade of dilator responses to outflowobstruction was greater than reduction in responses toa nonspecific dilator stimulus. This indicates thatphentolamine produced specific blockade of dilator re-sponses to outflow obstruction and supports the hy-pothesis that the dilatation results from withdrawal ofadrenergic constrictor tone. Activation of sympathetichistaminergic and cholinergic pathways apparently didnot contribute, because administration of tripelen-namine and atropine did not decrease the dilatation.

ACKNOWLEDGMENTSWe gratefully acknowledge the secretarial assistance of MIs.Julianne Garvey and Ms. Donna Thomas.

The study was supported by Clinical Investigatorships fromthe Veterans Administration; by Research Grants HL 02644,HL 09835, and HL 14388 and Research Career DevelopmentAward FIL-K4-28749 from the National Heart and LungInstitute; and by grants from the Iowa and American HeartAssociations.

REFERENCES1. Aviado, D. M., Jr., and C. S. Schmidt. 1959. Cardio-

vascular and respiratory reflexes from the left side ofthe heart. Amn. J. Physiol. 196: 726.

2. Salisbury, P. F., C. E. Cross, and P. A. Rieben. 1960.Reflex effects of left ventricular distention. Circ. Res.8: 530.

3. Ross, J., Jr., C. J. Frahm, and E. Braunwald. 1961.The influence of intracardiac baroreceptors on venousreturn, systemic vascular volume, and peripheral re-sistance. J. Clin. Izvest. 40: 563.

4. Mark, A. L., J. M. Kioschos, P. G. Schmid, D. D.Heistad, and F. M. Abboud. 1971. Vascular responses toexercise in aortic stenosis: Possible implication of ven-tricular baroreceptors. Clin. Res. 19: 644.

5. Calvelo, M. G., F. M. Abboud, D. R. Ballard, andW. Abdel-Sayed. 1970. Reflex vascular responses tostimulation of chemoreceptors with nicotine and cyanide.Circ. Res. 27: 259.

6. Hanley, H. G., J. C. Costin, and N. S. Skinner, Jr.1971. Differential reflex adjustments in cutaneous andmuscle vascular beds during experimental coronaryartery occlusion. Am. J. Cardiol. 27: 513.

7. Uvnds, B. 1954. Sympathetic vasodilator outflow. Phys-iol. Rev. 34: 608.

8. Beck, L. 1965. Histamine as a potential mediator ofactive reflex dilatation. Fed. Proc. 24: 1298.

9. Brody, M. J. 1966. Neurohomoral mediation of activereflex vasodilatation. Fed. Proc. 25: 1583.

10. Steel, R. G. D., and J. H. Torrie. 1960. Principles andProcedures of Statistics. McGraw-Hill Book Company,Inc., New York. 1st edition.

11. Abboud, F. M. 1972. Control of the various componentsof the peripheral vasculature. Fed. Proc. 31: 1226.

12. Bevegard, B. S., and J. T. Shepherd. 1967. Regulationof the circulation during exercise in man. Phlsiol. Rcv.47: 178.

13. Paintal, A. S. 1953. A study of right and left atrialreceptors. J. Physiol. 120: 596.

14. Coleridge, J. C. G., and C. Kidd. 1963. Reflex effects ofstimulating baroreceptors in the pulmonary artery. J.Physiol. 166: 197.

15. Heitz, D. C., R. A. Shaffer, and M. J. Brody. 1970.Active vasodilatation evoked by stimulation of sinusnerve in the conscious dog. Am. J. Physiol. 218: 1246.

16. Takeuchi, T., and J. W. Manning. 1971. Muscle cholin-ergic dilators in the sinus baroreceptor responses incats. Circ. Res. 29: 350.

Reflex Vascular Responses to Left Ventricular Outflow Obstruction 11,;3