Cardiovascular Reactivity toPsychosocial Stressors

A Review ofthe Effects ofBeta-Blockade

PAUL J. MILLS, PH.D.JOEL E. DIMSDALE, M.D.

Fifty-nine studies examining the effects ofbeta-blockers on cardiovascular reactivity topsychosocial stressors are reviewed. Across all classifications ofbeta-blockers, heartrate reactivity was reduced (p<O.OOOJ), while there were no significant changes in eithersystolic or diastolic blood pressure reactivity. Nonselective beta-blockers were moreoften associated with a reduction in heart rate reactivity than selective blockers(p<O.05). There was no evidence that drug lipophi/icity or intrinsic sympathomimetic ac­tivity differentially affected blood pressure or heart rate reactivity,. nor was there evi­dence that the reactivity ofhypertensive subjects was differentially affected by blockadecompared to the reactivity ofnormotensive subjects. While beta-blockers are effective inreducing resting blood pressure, they are not effective agents in reducing blood pressurereactivity to mild psychosocial stressors.

B eta-adrenergic receptor blocking drugs(beta-blockers) are widely used for the treat­

ment ofhypertension. I They are clearly effectivein reducing resting blood pressure and heart rate.Because increased blood pressure and heart ratereactivity may be related to subsequent cardio­vascular morbidity,2-S many have wondered ifbeta-blockers can reduce the amount of cardio­vascular reactivity to psychosocial stressors.

While it appears that beta-blockers are effec­tive in reducing heart rate reactivity,&-9 the datafor blood pressure reactivity are less consistent.In an attempt to clarify this issue, some investi­gators have contrasted the effects ofselective andnonselective beta-blockers on reactivity.6, 8-13 Intheory, beta) selective blockade should lowerheart rate reactivity without interfering with thevasodilatory function of peripheral beta2-adren­ergic receptors. Other investigators havecompared beta-blockers with intrinsic sympatho-

VOLUME 32 • NUMBER 2 • SPRING 1991

mimetic actIvIty (ISA) vs. those withoutISA.6

,.IO,11 Compared to beta-blockers with ISA,those without ISA would not be expected toactivate the peripheral beta2-adrenergic vasodila­tory receptors. We examined these issues furtherby reviewing studies that investigate the effectsof beta-blockers on reactivity to psychosocialstressors.

METHODS

Studies included in this review were locatedthrough a MEDLARS literature search, corre-

Received November 9, 1989; revised February 14,1990; accepted March 77 1990. From the Department ofPsychiatry7 University of California, San Diego. Addressreprint requests to Dr. Mills, V.C.S.D. (T-004)7 La Jolla, CA92093-0804.

Copyright © 1991 The Academy of PsychosomaticMedicine.

209

Effects of Beta-Blockade

210 PSYCHOSOMATICS

TABLE 1. Properties of beta-blocking drugs employed i n the studies reviewed

Drug Selectivity ISAa Solubility

Propranolol Nonselective None LipophilicMepindolol Nonselective High Lipophilic

Pindolol Nonselective High Lipophilic

Oxprenolol Nonselective Low Lipophilic

Atenolol Selective None Hydrophilic

Metoprolol Selective None Lipophilic

Timolol Nonselective None Lipophilic

Prizidilol Nonselective None Lipophilic

aISAinth nsic sympathomimetic activity.

spondence with other investigators, reprint files,

and a thorough evaluation of the bibliographies

oflocated studies. Our review focuses on the type

of stressor, the drug classification, the study de-

sign, and the drug effect on cardiovascular reac-

tivity.

The stressors used in these studies are di-

verse, and they fall into two main categories:

naturalistic and laboratory-based stressors. The

naturalistic stressors include automobile driving,

simulated flight, anticipation of skiing competi-

tion, performance of surgery, undergoing sur-

gery, public speaking, and public musical

performance. The laboratory stressors include

several variations of mental arithmetic, reaction

time, video game, interview, a sorting task, pat-

tern recognition, and the Stroop color word frus-

tration task.

The various beta-blockers used in the studies

are listed in Table 1. Each drug has been identi-

fied according to three properties: specificity

(beta, selective or nonselective), solubility (hy-

drophilic or lipophilic), and ISA (none, low, or

high). These three properties are evaluated sepa-

rately for their effects on reactivity.

Finally, we applied a goodness-of-study

index to each study.’4 We used a weighting sys-

tem whereby one point was awarded for every 20

subjects studied. Additional points were given

for each of the following components: 1) ran-

domization, 2) at least single blinding, 3) a cross-

over design, and 4) validity data showing that the

task induced increased cardiovascular reactivity

under placebo conditions. Thus, a study could

receive up to four points for design, plus addi-

tional points for sample size.

RESULTS

A total of59 articles published between 1967 and

1989 were located. The studies are summarized

in Table 2 in chronological order. For studies

using more than one type ofpsychosocial stressor

and/or drug, the results are presented separately

if the drug effects were different for each task.

Sample size, research design, and the drugs

used were highly variable. Sample size ranged

from 6 to 88 subjects, with a mean±SD of

26.9±18. The goodness-of-study index had a

wide range, from a low of 2 to a best score of 7,

with a mean of 3.81±0.99.

Statistical methods varied as well. These

included analysis of variance and covariance,

delta scores, and percent delta scores. There is

some controversy regarding the merits of these

various methods as applied to reactivity re-

search.�’67 We used the authors’ statistical results

as the sole basis for reporting the data. Nearly all

of the studies reported that active drug decreased

blood pressure and heart rate levels during both

rest and stress conditions. A drug effect on reac-

tivity was considered present when there was a

significant change in the difference between the

stress level minus the rest level.

Three studies were excluded from the anal-

yses for one or more of the following reasons:

insufficient information regarding the beta-

blocking agent, insufficient statistical informa-

tion, or a design that did not adequately permit

assessment of the effect of beta-blockade alone

on reactivity.”61’M

In evaluating drug effects on reactivity, the

total number of tasks tested across the studies was

TABLE 2. Studies examining the effects ofbeta-blockade on cardiovascular reactivity to psychosocial stressors

SourceStudy N Design

Design Score Drug & Dosage Task SBP DBP HR

Eliasch’5 Propranolol, 5.0 mg iv Simulated NC NC DEC

12 Nor,3 Hyp flight

CO 2

Nicotero’6 Propranolol, 120 mg tid, Noxious NC in MAP DEC

1 1 Hyp 10-16 days stimuli

SB,CO 3

Imhof17 Oxprenolol, 40 mg qd, lday Skiing - - DEC9 UNSP

R,DB,CO 4

Ulrych’8 Oxprenolol, 5 mg iv Public speaking NC NC NC

14 Nor, 33 Hyp

R 4

Taggart’9 Oxprenolol, 40 mg qd, I day Auto - - DEC7 Nor driving

SB,CO 3

Tarazi�� Propranolol, 40-80 mg, 4xday, Having NC NC NC

52 Hyp 4-34 months BP taken

CO 4

Taylor�’ Oxprenolol, 40 mg qd, 1 day Auto - - DEC6Nor driving

R,DB,CO 4

Taggart22 Oxprenolol, 40 mg qd, 1 day Public speaking - - DEC23 UNSP

R,DB,CO 5

Obrist� Propranolol, 4 mg iv Reaction - - NC

32UNSP time

R,SB 4

Guazzi24 Propranolol, 330 mg/day, Math DEC DEC DEC

l4Hyp 3wks

SB 2

Aronow� Propranolol, 240 mg/day Mental NC NC DEC

20 Hyp Timolol, 30 mg/day, 5 wks stress of

R,DB,CO 5 cardiaccatheterization

Taggart� Oxprenolol, 40 mg qd, 1 day Dental - - DEC21 Nor procedure

R,DB 4

Siitonen27 Oxprenolol, 40 mg qd, 1 day Bowling NC NC DEC

17 Nor competition

R 3

James� Oxprenolol, 40 mg qd, 1 day Stage fright NC NC DEC

24 Nor

R,DB,CO 5

Nyberg29 Propranolol, 160 mg qd, 12 wks Math NC NC DEC

6 Nor, 10 Hyp Metoprolol, 200 mg qd, 12 wi’s

R,SB,CO 4

Heidbreder�0 Metoprolol, 100 mg qd,�1&6 wks Public speaking NC NC DEC

50 Nor,20 Hyp

R,DB,CO 7

VOLUME 32 #{149}NUMBER 2 #{149}SPRING 1991 211

Mills and Dimsdale

(continued)

TABLE 2. Studies examining the effects of beta-blockade on cardiovascular reactivity to psychosocial stressors

Source

Study N Design

Design Score Drug & Dosage Task SBP DBP HR

Sorting

task

Shock

avoidance

reaction

time

Performing

surgery

Stage

fright

Math

Math

Stage

fright

Math

Math

Auto

driving

Noise

DEC DEC -

DEC NC DEC

DEC INC DEC

- - DEC

NC NC DEC

NC NC DEC

NC INC NC

- - NC

NC NC NC

NC NC DEC

NC NC NC

NC NC NC

NC NC NC

INC NC NC

Propranolol, 120 mg/day, 6 wks

4

Propranolol, 4mg iv

3

Oxprenolol, 40mg qd, 1 day

2

Oxprenolol, 40mg, 1 day

4

Propranolol, 15 mg iv

Mepindolol, 0.5 mg iv

4

Oxprenolol, 100mg qd, 8 wks

Propranolol, 100mg qd, 8 wks

4 Pindolol, 100mg qd, 8 wks

(as compared to atenolol)

Propranolol, 40mg qd, 1 day

3

Atenolol, 100 mg, qd, 8 wks

3

Propranolol, 0.1 mg/kg iv

Metoprolol, 0.2 mg/kg iv

4

Oxprenolol, 331 mg/day, 16 wks

2

Metoprolol, 0.2 mg/kg iv

Propranolol, 0.1 mg/kg iv

3

Propranolol, 80mg tid, 5 wks

Oxprenolol, 80mg tid, 5 wks

4

Propranolol, NR

3

Propranolol, 112mg/day

3

Mepindolol, 0.5 iv

Propranolol, 15 iv

3

Mental NC NC DEC

stress of

cardiac

catheterization

Math,competition

Interview

Math

NC INC DEC

NC NC DEC

NC NC DEC

212 PSYCHOSOMATICS

Effects of Beta-Blockade

Dunn3’

21 Hyp

SB,CO

Obrist32

20 Nor

SB

Foster33

8 UNSP

NR

James34

24 UNSP

R,DB

Bonelli10

12 Nor

R,SB,CO

Waal-Manning”

27 Hyp

R,CO

Brantigan35

8 UNSP

DB,CO

Waal-Manning�

10 Hyp

R, SB,CO

Andren37

13 Hyp

R,DB,CO

Millar-Craig38

15 Hyp

OD

Andren12

9 Hyp

R,DB,CO

Ferlinz39

20 Hyp

R,DB

Light4#{176}

12 Nor

R,SB

Krantz41

88 Other

OT

Bonelli42

10 Nor

SB,CO

TABLE 2. Studies examining the effects of beta-blockade on cardiovascular reactivityto psychosocial stressors

(continued)

SourceStudy N Design

Design Score Drug & Dosage Task SBP

NC in

DBP

MAP

HR

Brantigan43

29 UNSP

DB,CO

Neftel�

22 Nor

R,DB

Levander45

12 Nor

R,DB,CO

Caldari�

20 Hyp

CO

Houben13

22 Hyp

DB,CO

James47

30 UNSP

R,DB,CO

Schmieder’�

19 Hyp

R,CO49

Bnsse40 UNSP

R,DB

Francois50

15 Hyp,16 Nor

CO

Eggersten5’

9 Hyp

SB,CO

Floras6

35 Hyp

R

Langer52

34 Nor

R

Sherwood7

28 Nor

SB,CO

Gatchel53

10 Other

R

AlbusM

48 Nor

R,DB

Stage fright

Stage fright

Digit-span

Math

Math

Stage fright

Interview

Oral surgery

Math

Stroop test

Noise

Math

Reaction

time

Reaction

time

Reaction

time

Public speaking

Math,

noise

DEC

- - DEC

- - DEC

NC INC DEC

NC NC DEC

DEC NC DEC

DEC DEC DEC

NC NC DEC

NC NC NC

NC NC DEC

NC NC NC

DEC NC DEC

NC NC DEC

NC NC DEC

NC NC DEC

NC DEC DEC

NC NC DEC

NC NC DEC

NC NC DEC

- - DEC

NC NC DEC

DEC NC DEC

- - DEC

- - NC

VOLUME 32- NUMBER 2 #{149}SPRING 1991 213

Propranolol, NR

4

Atenolol, 100mg qd, I day

4

Propranolol, 40mg qd, 1 day

Metipranolol, 5-20mg qd, I day

4

Prizidilol, 200-400mg bid,

6 wks

3

Metoprolol, 100mg tid, 4 wks

Propranolol, 80mg tid, 4 wks

4

Pindolol, 5 mg qd, 1 day

5

Atenolol, 100mg, 4 wks

4

Pindolol, 5 mg, 1 day

Metoprolol, 100mg, 1 day

5

Atenolol, 100mg qd, 7 wks

3

Propranolol, NR

3

Atenolol, 100mg qd, 20 wks

Metoprolol, 200mg qd, 20 wks

3 Pindolol, 15 mg qd, 20 wks

Propranolol, 160mg qd, 20 wks

Atenolol, 100mg qd, 20 wks

Metoprolol. 200mg qd, 20 wks

Pindolol, 15 mg qd, 20 wks

Propranolol, 160mg qd, 20 wks

Propranolol,4 mg iv

3

Propranolol, 4 mg iv

4

Propranolol, 40mg qd, 2-3 wks

2

Pindolol, 4 mg, 1 day

5

Mills and Dimsdale

TABLE 2. Studies examining the effectsof beta-blockade on cardiovascular reactivity to psychosocial stressors

5

Eliasson57

47 Hyp

R

NC INC DEC

NC NC DEC

INC NC NC

NC NC NC

Mazzuero59

64 Other

R

Ward�

62 Hyp

DB

46 Hyp

R,DB

Freyschuss9

30 Nor

R,DB,CO

Ruddel61

63 Hyp

R

5

5

S

Oxprenolol, 320 mg/day

DEC

Math

Albus63

44 Nor

R,BD

DelamaterM

30 Nor l2Hyp

NC NC

S

3

Reaction

time

NC

DECDEC INC

214 PSYCHOSOMATICS

Effects of Beta-Blockade

(continued)

Source

Study N DesignDesign Score Drug & Dosage

Atenolol, 100mg qd, 4 wks

Task

Math

SBP

-

DBP

-

HR

DECWu55

27 Hyp

R,DB,CO

Krantz56 Propranolol, 3 mg iv

12 Nor

DB,CO 3

4

Math, NC NC DEC

interview

Propranolol, 80mg bid, 24 wks Stroop test NC NC DEC

Metoprolol, 100mg bid, 28 wks

Schmieder5t Oxprenolol, 160mg qd, 28 wks Math40 Hyp

R,CO S

Propranolol, 40mg tid, 2 days Math,

Atenolol, 100mg qd, 2 days sentence

5 completion

Atenolol, 50mg qd, 2 wks Math,

Metoprolol, 100mg qd, 2 wks reaction

5 time,video

game, pattern

recognition

Atenolol, 50mg bid, 4 wks Math, NC NC DEC

Propranolol. 80mg bid, 4 wks interview

Metoprolol, 0.15 mg/kg iv Stroop test NC NC

Propranolol, 0.15 mg/kg iv

Weber62 Atenolol, 50mg/day, 3 wks

12 Hyp

R,DB,CO 4

Math NC NC DEC

Propranolol,40 mg qd, 1 day Math, NC NC DECCGP361A,4&l0mgqd, 1 day noise

NR Role playing NC NC

Light65 Propranolol, 0.06 mg/kg iv

29 Nor 11 Hyp

SB 4

Note: Study Design: R indicates random; DB=double-blind SB=single-blind; CO=crossover, OT=open trial;NR=not reported.

Dependent Variables: SBP=systolic blood pressure; DBP=diastolic blood pressure; HR=heart rate; MAP=meanarterial pressure.

Subjects: Nor=normotensive; Hyp=hypertensive; Other=postmyocardial infarct patients; UNSP=unspecified.

Reactivity Results: NC=no change; INC=increase; DEC=decrease; -=not measured.

....

Mills and Dimsdale

TABLE 3. Beta-blocking drugs by classillcatlon: number of WIts examining blood pressure reactivity topsycbosodal stressors

SystolkBP DiastolkBP

Number ofTasks (%) Number of Tasks (%)

Drug Type Increase Decrease No Change Increase Decrease No Change

Selective 1(3.8) 2 (7.7) 23 (88.5) 0 2 (18.0) 23 (92.0)Nonselective I (1.9) 7 (13.7) 43 (84.3) 6 (11.5) 2 (3.8) 44 (84.6)

ISA 0 I (8.3) II (91.7) 1(7.7) 0 12 (92.3)NolSA 2 (3.0) 8 (12.3) 55 (84.6) 5 (7.8) 4 (6.2) 55 (86.0)

Lipophilic I (1.5) 7 (10.7) 57 (87.7) 6(9.2) 2 (3.0) 57 (87.7)Hydrophilic I (8.3) 2 (16.6) 9 (75.0) 0 2 (16.6) 10 (83.4)

Total 2 (2.6) 9 (11.6) 66 (85.7) 6 (7.8) 4 (5.2) 67 (87.0)

Note: ISA=intrinsic sympathomimetic activity.

Heart Rate

Note: No increases were reponed; ISA=intrinsicsympathomimetic activity.

TABLE 4. Beta-blocking drugs by classific:atlon:number of tasks examining heart ratereactivity to psychosocial stressors

used. Thus, for studies using more than one taskand/or drug, results are included for each in­stance. The articles produced a total of 77 obser­vations evaluating drug effects on blood pressurereactivity. Regardless of drug classification, forsystolic blood pressure, a total of 66 (85.7%)observations showed no change; 2 (2.6%)showed an increase; and 9 (11.6%) showed adecrease in reactivity. For diastolic blood pres­sure, 67 (87.0%) tasks showed no change; 6(7.8%) showed an increase; and 4 (5.2%) showeda decrease in reactivity.

For heart rate, a total of90 observations weregenerated. Regardless of drug classification, 16(17.7%) observations showed no change; none

showed an increase; and 74 (82.3%) showed adecrease in reactivity.

Tables 3 and 4 present a summary of drugeffects on blood pressure and heart rate reactivity,respectively, according to the three classifica­tions delineated in Table I. For each dependentvariable, separate chi-square statistical tests wereused to examine drug effects on reactivity.68 Theresults indicated that there were no significanteffects of beta-blockade on blood pressure reac­tivity; nor were there any significant differenceswithin the three drug classifications on reactivityfor either systolic (X2<2.30; df=2; p>O.31) ordiastolic (X2<4.6; df=2; p>O.1 0) blood pressure.For heart rate, regardless of drug classification,beta-blockade was associated with a significantreduction in reactivity (p<O.OOOOI). There wasalso a significant association between drug selec­tivity and reactivity (X2=4.23; df=l; p=O.039),indicating that nonselective blockers were moreoften associated with a decrease in heart ratereactivity than selective blockers. Neither ISAnor solubility affected heart rate reactivity(X2=0.23; df=l; p=0:63 and X2=0.29; df=l;p=O.58, respectively).

We wondered whether the quality of thestudy was a significant factor influencing theresults. To address this, we compared the meangoodness-of-study design score in studies thatreported an increase, decrease, and no change inblood pressure reactivity. Since for heart rate, nostudies reported an increase, we compared stud-

Number of Tasks (%)

18 (69.3) 8 (30.7)56 (87.5) 8 (12.5)

18 (85.7) 3 (14.3)56 (81.2) 13 (18.8)

64(83.1) 13(16.8)10 (77.0) 3 (23.0)

74 (82.3) 16 (17.7)

Decrease No Change

ISANolSA

LipophilicHydrophilic

Total

SelectiveNonselective

Drug Type

VOLUME 32 - NUMBER 2 - SPRING 1991 215

TABLES. Goodness-of-study design score for eachdependent variable grouped accordingto the effectof beta-blockade on reac-tivity

Variable Increase Decrease No Change

Systolic BP 4.0±1.41 3.30±1.02 3.78±1.04

Diastolic BP 3.6±0.89 3.25±0.95 3.76±1.06

Heart Rate 3.84±1.03 3.70±0.95

Note: Values are means±SD.

Effects of Beta-Blockade

216 PSYCHOSOMATICS

ies reporting a decrease or no change in reactiv-

ity. Analysis of variance indicated that there were

no significant differences in the quality of the

studies for any dependent variable (F<0.69;

p>.O.Sl) (see Table 5).

There is a body of literature suggesting that

hypertensive subjects differ in their cardiovascu-

lar reactivity compared to normotensive sub-

jects.3 We examined the cardiovascular reactivity

response to beta-blockade to see whether it dif-

fered in the normotensive and hypertensive sub-

jects. The number of observations of increase (for

blood pressure only), decrease, or no change in

reactivity was compared for each variable ac-

cording to diagnosis. The results indicated that

there were no differences between the two groups

for systolic (X2=O.1 9; df=2; p=033), diastolic

(�2=�-�2; df=2; p=0.l7), or heart rate (x2=0.30;

df=l; p=O.7l) reactivity.

DISCUSSION

In general, the results suggest that beta-blockers

do not significantly change blood pressure reac-

tivity to mild psychosocial stressors. On the other

hand, heart rate reactivity is reduced (approxi-

mately 13 bpm). Nonselective beta-blockade was

found to be more often associated with a reduc-

tion in heart rate reactivity than selective beta-

blockade. Whether or not this is a chance

observation is unclear. We did indirectly investi-

gate whether this finding was a result of a differ-

ence in drug potencies between the two classes

of drugs. We compared the mean drug dosage of

the two most widely used selective and nonselec-

live beta-blockers in the studies that showed a

decrease in heart rate. Propranolol had a mean

dosage of 1 16±80 mg and metoprolol a mean

dosage of 142±53 mg. Although exact dose-

equivalency data are not established between

these two classes of drugs, propranolol is gener-

ally considered to be weaker than metoprolol in

its beta-blocking effect. Thus, it appears that the

finding is not due to a disproportionately higher

potency of the nonselective compared to the se-

lective blockers.

Theoretically, one might envision that non-

selective beta-blockers could reduce heart rate

reactivity more effectively than selective block-

ers because both beta,- and beta2-adrenergic re-

ceptors are found in the human atria and

ventricles.�’7#{176} Nonselective blockade inhibits

both beta-adrenergic receptors. Selective block-

ade leaves the beta2-adrenergic receptors avail-

able for agonist binding and continued

moderation of heart rate.71’72 Brodde et al.73 sug-

gest that under normal conditions heart rate is

controlled by norepinephrine acting selectively

on cardiac beta,-adrenoreceptors. However,

under conditions of stress and the increased sym-

pathetic activation of both norepinephrine and

epinephnne, additional stimulation of beta2 re-

ceptors contributes to both heart rate and con-

tractility.73

Beta-blockers with ISA, as compared to

those without ISA, would presumably stimulate

the vasodilatory function of beta2-adrenergic re-

ceptors during reactivity.74 However, there were

no significant differential effects of ISA on reac-

tivity.

One study compared aselective beta-blocker

to three nonselective beta-blockers, with no pla-

cebo control. The nonselective blockers led to an

increased diastolic blood pressure reactivity

compared to the selective blocker.” This is in

contrast to other studies, which, in the context of

placebo control, also compared selective and

nonselective beta-blockers; these studies found

no difference in blood pressure reactivity.8’9”3’2”9

Some of the studies in this review also eval-

uated the effects of beta-blockade on exercise

reactivity. In examining these data, it appears that

the effects of beta-blockade on exercise reactivity

are similar to the effects of beta-blockade on

psychosocial reactivity for heart rate and dia-

V

VOLUME 32- NUMBER 2- SPRING 1991 217

Mills and Dimsdale

stolic blood pressure, but not for systolic bloodpressure. Beta-blockade is generally,6’50’52’M’75’76

although not consistently,36’55 associated with a

reduction in heart rate response to dynamic exer-

cise. Diastolic blood pressure reactivity to

exercise remains unchanged with beta-block-

ade.6’M’5�.SS63lS�l6While beta-blockade has no sig-

nificant effect on systolic blood pressure

reactivity to psychosocial stressors, it reduces the

systolic blood pressure increase resulting from

exercise.6’5#{176}’55’63’7�78Normally with exercise, di-

astolic blood pressure remains unchanged or de-

creases slightly while heart rate and systolic

blood pressure increase profoundly.6’50’63’78 Thus,

it appears that more intense sympathetic activa-

tion, such as with exercise, is necessary for beta-

blockade to attenuate the blood pressure response

to stress.

What are the mechanisms involved in main-

taining blood pressure reactivity when heart rate

reactivity is reduced? Normally, psychosocial

stressors will increase cardiac output approxi-

mately 35%-40% and decrease peripheral re-

sistance approximately 10%-iS % 7-9.15.37,42.58

References

During psychosocial stress with beta-blockade,

heart rate is generally decreased, yet there is a

compensatory increase in peripheral resistance of

approximately 1 0%-iS %7_1o�1s�37�42�s8 The in-

creased resistance may result from unopposed

stimulation of alpha,- and alpha2-adrenergic re-

ceptors by epinephrine, which generally in-

creases during beta-blockade and psychosocial

stress.9”#{176}’37’�’49’63Central cardiovascular control

during psychosocial stress, therefore, appears to

be geared more toward preservation of blood

pressure than heart rate.79

In summary, although beta-blockade ther-

apy does reduce heart rate reactivity, it does not

appear to significantly change blood pressure

reactivity to mild psychosocial stress. Neither

drug solubility nor ISA significantly affects

blood pressure or heart rate reactivity.

This work was supported in part by grants

MO1-RR00827, HL36005 , and HL4OlO2from the

National Heart, Lung, and Blood Institute. The

authors wish to thank Sandra Delehanty and

Charles Berry, Ph.D. ,for assistance.

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