CR and our baroreflex

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Hi All,

As a definition, see:

baroreflex = A negative feedback system which buffers

short-term changes in blood pressure. Increased pressure

stretches blood vessels which activates pressoreceptors

(baroreceptors) in the vessel walls. The net response of

the central nervous system is a reduction of central

sympathetic outflow. This reduces blood pressure both by

decreasing peripheral vascular resistance and by lowering

cardiac output. Because the baroreceptors are tonically

active, the baroreflex can compensate rapidly for both

increases and decreases in blood pressure.

CR, it seems, leads to an improvement in this negative

feedback system, the baroreflex, so that we " can

compensate rapidly for both increases and decreases in

blood pressure " .

There seems to have been some discussion regarding this

topic, and it seemed that the consensus was that some had

a worse baroreflex with CR, but most CRers found that

there was an improvement.

See the pdf-available below.

Alvarez GE, Davy BM, Ballard TP, Beske SD, Davy KP.

WEIGHT LOSS INCREASES CARDIOVAGAL BAROREFLEX FUNCTION IN

YOUNG AND OLDER OBESE MEN.

Am J Physiol Endocrinol Metab. 2005 Jun 7; [Epub ahead of

print]

PMID: 15941781

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstra\

ct & list_uids=15941781 & query_hl=7

INTRODUCTION

Abrupt decreases and increases in systolic arterial blood

pressure produce baroreflex mediated

shortening and lengthening, respectively, of the R-R

interval (7). This phenomenon is best described by

the sigmoidal relationship between R-R interval length

and systolic blood pressure and is otherwise

known as the cardiovagal baroreflex. The linear portion

of this relation is used to derive the gain or

sensitivity of the cardiovagal baroreflex.

Cardiovagal baroreflex sensitivity (BRS) declines (6, 12,

13) and total and abdominal adiposity

increases (8, 19, 24) with advancing age. Importantly,

reduced cardiovagal baroreflex sensitivity has been

associated with poor orthostatic tolerance in older

adults (23) and an increased risk of cardiac sudden

death in post-myocardial infarction patients (16, 17).

We (1, 3) and others (9, 11) have observed reduced

cardiovagal BRS in overweight and obese

humans, particularly in those with elevated abdominal

visceral fat (1, 3). In addition, total body and

abdominal adiposity are important physiological

correlates of reduced cardiovagal BRS in older adults

.... All subjects were normotensive

(arterial blood pressure <140/90 mmHg) and free from

overt cardiovascular diseases as determined

from individual health histories. Subjects were further

evaluated for the presence of overt

cardiopulmonary disease by resting and maximal exercise

electrocardiograms. These individuals

were nonsmokers, non-diabetic (2-hr post glucose load

<200 mg/dL) and not taking any medications

that could influence autonomic-circulatory function. All

subjects were sedentary and not

participating in any program of regular physical activity

(defined as >20 min on more than 2

days/wk).

.... RESULTS

Subjects Characteristics.

The characteristics of the subjects are displayed in the

Table. There was an

approximate 12 and 36 year age difference between the

NO-Y and the OB-Y and OB-O, respectively.

Body mass, body mass index, body fat %, fat mass, fat

free mass, total abdominal fat, subcutaneous fat,

visceral fat, systolic blood pressure and diastolic blood

pressure were all similar in the OB-Y and OB-O,

but higher in these groups compared with the NO-Y (all

P<0.05). Maximal oxygen consumption was

~26-35% lower (P<0.05) in the OB-O compared with both

OB-Y and NO-Y (both expressions). In

addition, maximal oxygen consumption was lower (P<0.05)

in OB-O compared with NO-Y, regardless of

expression. RR interval (and heart rate) at rest was

similar among the groups (all P>0.05).

Table. Subject Characteristics at Baseline and Following

Weight Loss

-------------------

Variable Nonobese Young (n=13) Obese Young Baseline

(n=10) Obese Young Weight Loss (n=10) Obese Older

Baseline (n=6) Obese Older Weight Loss (n=6)

-----------------------

Age (years) 21.1±1.0 32.9±2.3* -- 60±2.7* --

Height (cm) 182.9±2.6 179.3±2.3 -- 177.6±3.2 --

Body Mass (kg) 71.6±2.4 97.9±4.3* 90.2±3.8 91.2±4.1*

83.9±4.0**†

Body Mass Index (kg/m 2 ) 21.5±0.5 30.4±1.0* 28.0±1.0

28.9±1.1* 28.1±1.4

Body Fat (%) 16.4.0±1.3 28.0±1.5* 25.9±1.4 27.9±2.0*

24.9±2.8**†

Fat Mass (kg) 11.8±1.1 27.6±2.4* 23.5±1.9 25.7±2.7*

21.2±3.1**†

FFM (kg) 56.5±0.8 67.0±2.4* 63.4±2.3 62.7±2.5*

59.2±2.3**†

Total Abdominal Fat (cm 2 ) 184±16 471±37* 393±32 516+56*

414+63**†

Subcutaneous Fat (cm 2 ) 131±13 337±31* 286±25 333+58*

274±47**†

Visceral Fat (cm 2 ) 53±4 135±17* 107±14 184±27*

140+31**†

VO2 Max (ml/kg/min) 52.4±1.8 40.3±2.6* 44.4±2.3 32.6±1.0*

35.0±1.7**†

VO2 Max (ml/kgFFM/min) 66.3±2.0 58.3±2.8* 62.4±2.2

47.6±2.3* 49.2±2.5**†

SBP (mmHg) 116±2 124±2* 121±3 121±2* 111±5**†

DBP (mmHg) 64±1 72±3* 70±3 76±2* 70±2**†

RR Interval (ms) 1047±50 1071±26 1002±55 950±12 1062±41

Heart Rate (bpm) 57±2 64±3 61±3 57±2 57±2

---------------------------

Values are means±SE.

*P<0.05 vs. Nonobese Young Men; ** = significant group

effect; † = significant time effect.

FFM=fat free mass; SBP=systolic blood pressure;

DBP=diastolic blood pressure.

Effects of Weight Loss on Selected Subject

Characteristics.

The changes in selected subject

characteristics with weight loss are shown in the Table.

Body mass, body fat percentage, fat mass, fat free

mass, and total abdominal, visceral, and subcutaneous fat

were reduced following weight loss in the OB-Y

and OB-O (all P<0.05). Maximal oxygen consumption,

expressed relative to body weight, increased

(P<0.05) following weight loss in OB-Y and OB-O. However,

there was no significant change in

maximal oxygen consumption when expressed relative to fat

free mass. Maximal oxygen consumption

adjusted for the level of fat free mass (ANCOVA) also did

not change with weight loss in the two groups

(P>0.05). Both systolic and diastolic blood pressure

decreased (P<0.05) following weight loss in these

men; the decrease in systolic and diastolic blood

pressure tended (both P=0.11) to be larger in the older

men. However, there was no change in resting RR interval

(or heart rate) (P>0.05) following weight loss.

Effect of Weight Loss on the Cardiovagal Baroreflex.

Prior to weight loss cardiovagal BRS was ~35 and

~60% lower (both P<0.05) in OB-Y and OB-O compared with

NO-Y (11.5±1.9 vs. 6.7±1.2 vs. 17.5±2.2

msec/mmHg) (Figure 1). Cardiovagal BRS was lower (P<0.05)

in OB-Y compared with OB-O (Figure

1). The operating range was ~50% lower (172±28 vs. 370±90

ms, P=0.054) (Figure 2) in the OB-O

compared with young men (Figure 2), but did not differ

significantly between OB-Y and OB-O (P=0.14).

Cardiovagal BRS increased to 18.5±2.6 and to 12.8±4.2

msec/mmHg in the OB-Y and OB-O (both

P<0.05), respectively, due to changes in both the

saturation and threshold regions data not shown.

Following weight loss, cardiovagal BRS in the young and

older obese/overweight men was ~105% and

~75% (P>0.05) of that observed in NO-Y (Figure 1). The

operating range increased to 356±57 and

356±78 ms in the OB-Y and OB-O (P<0.05), respectively.

Following weight loss, the operating range of

both the overweight/obese young and older men was ~95%

(P>0.05) of the levels observed in the young

men (Figure 2). The operating point was similar in the

three groups, but was shifted significantly towards

higher systolic blood pressures in the OB-Y and OB-O

compared with NO-Y, i.e., to a lower level of

systolic BP after weight loss. The results were identical

when heart rate was used as the efferent response

variable instead of R-R interval (data not shown).

Correlates of the Increase in Cardiovagal BRS and

Operating Range with Weight Loss.

There were no

significant correlates of the improvements in cardiovagal

BRS or operating range with weight loss.

DISCUSSION

The new and important finding of this investigation was

that the sensitivity and operating range of

the cardiovagal baroreflex increased dramatically

following modest weight loss in overweight/obese

young and older adults. In addition, the operating point

of the cardiovagal baroreflex was shifted toward

lower blood pressures in both groups. Interestingly, the

sensitivity and operation range of the cardiovagal

baroreflex in overweight/obese young men following weight

loss was similar to that observed in

nonobese young men. However, cardiovagal baroreflex BRS

and operating range remained lower in

overweight/obese older men following weight loss compared

with the nonobese young men.

The increase in cardiovagal baroreflex sensitivity with

weight loss in the young and older men

from the present study is consistent with that reported

by Grassi et al. (10) in young severely obese men

and women. Our findings extend these previous

observations in a number of important aspects. First, the

results of the present study suggest that weight loss

also increases cardiovagal BRS in older adults, a

population with particularly low levels of cardiovagal

BRS (6, 12, 13). Importantly, the increase in

cardiovagal baroreflex sensitivity can be achieved in

these individuals with mild to moderately obese

individuals who undergo only modest weight loss.

Second, the results of the present study suggest that the

operating range of the cardiovagal

baroreflex is also increased following weight loss in

both young and older men. To our knowledge, we

are the first to report an increase operating range of

the cardiovagal baroreflex with a non-pharmacological

in adults of any age. This is an important observation

because the operating range of the

cardiovagal baroreflex is reduced with advancing age

(22). Taken together with the increase in

cardiovagal BRS with weight loss, these observations may

have important implications for arterial blood

pressure regulation in older adults. Whether weight loss

is associated with improved orthostatic tolerance

in older adults is unknown.

The mechanism(s) responsible for the increase in

cardiovagal BRS remains unclear. However,

there are several possibilities. First, arterial

stiffness is an important determinant of cardiovagal BRS

(14). Thus, it is possible that improvements in

cardiovagal BRS with weight loss may be due, at least in

part, to corresponding reductions in arterial stiffness.

Second, it is possible that changes in one or more

factors that determine the transduction of

barosensory stretch into cardiac vagal outflow (e.g.,

sensitization of vagal afferents, alterations in central

integration, and/or increases in the number or

sensitivity of muscarinic receptors) may contribute to

increases in cardiovagal BRS with weight loss.

Finally, oxidative stress is elevated in obese older

adults (15) and weight loss reduces oxidative

stress (4) The results of a recent study suggests that

ascorbic acid infusion improves cardiovagal BRS in

older adults (21). Thus, it is possible that the increase

in cardiovagal BRS with weight loss may be due, at

least in part, to a reduction in oxidative stress. Future

studies will be necessary to explore these

possibilities.

Following weight loss, cardiovagal BRS remained lower in

the overweight/obese older compared

with nonobese young men. In contrast, cardiovagal BRS was

similar following weight loss in the

overweight/obese compared with nonobese young men. The

lack of correlation between increases in

cardiovagal BRS and changes in total body and abdominal

fat in overweight/obese young or older men

(or in the pooled sample of overweight/obese men)

suggests that factor(s) other than loss of body fat

is(are) important in contributing to increases in

cardiovagal BRS. The increase in cardiovagal BRS and

operating range observed with weight loss may be an acute

aftereffect of the negative energy balance

imposed by caloric restriction. We believe this is

unlikely because our subjects were studied after their

reduced body weight had been maintained for a one month

period. However, it is possible that the

magnitude of increase in cardiovagal BRS may have been

smaller or altogether absent with a longer

period of weight stability. This is an interesting

possibility needing further exploration.

There are at least two other possibilities that could

account for the remaining difference in

cardiovagal BRS following weight loss between the

overweight/obese older and nonobese young men for

this observation. First, the difference may be attributed

to the fact that body fat and regional fat

distribution were not “normalized” with caloric

restriction in the older men. Thus, larger increases in

cardiovagal BRS may be observed with a more substantial

weight loss in the older men. Second, the

difference in cardiovagal BRS following weight loss in

the overweight/obese older men and nonobese

young men may be due to biological aging per se. Future

studies will be necessary to clarify this issue.

The increase in cardiovagal BRS weight loss in the

present study was quite large (~60-90%)

compared with that achieved by regular aerobic exercise

training in older men (~25%) (20). We

recognize that it is difficult to make direct comparisons

across different studies. However, taken together

our findings suggest that weight loss is a highly

effective strategy to increase cardiovagal BRS in (young

and) older men. Whether the combination of weight loss

with regular aerobic exercise provides an

additional benefit is unknown but futures should be

designed to address this issue.

The major limitation of the present study is the small

sample size and lack of a control group.

Future studies with larger sample sizes and a control

group will be necessary to confirm or refute our

findings as well determine the mechanism(s) responsible

for the increase in cardiovagal BRS.

In summary, the results of the present study suggest that

weight loss improves cardiovagal

baroreflex function in young and older overweight/obese

men. Importantly, the increase in cardiovagal

baroreflex function was observed in overweight/obese men

exhibiting only moderate levels of weight

loss. ...

Al Pater, PhD; email: old542000@...

__________________________________

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