Dynamic Cardiovascular Responses to Infusions
of Atrial Natriuretic Factor in Humans
THOMAS J. EBERT, MEREDITH M. SKELTON, AND ALLEN W. COWLEY J R .
With the technical assistance of Doris U. Kreis
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SUMMARY We sought to demonstrate a hypotensive effect from infusions of atrial natriuretic
factor (ANF) into humans and to describe the mechanism(s) of this effect. Cardiovascular and
hormonal responses to human ANF-(99-126) (125 ng/kg bolus followed by a 30-minute infusion at 25
ng/kg/min) were determined in eight conscious volunteers and compared with responses of eight timecontrol subjects who received isotonic saline. Baseline levels of ANF (52.8 ± 5.5 pg/ml) increased 8.8fold after 30 minutes of ANF infusion but were unchanged in the time controls. Plasma levels of renin,
aldosterone, vasopressin, sodium, potassium, and osmolality did not change during infusions. A
transient 5% reduction in mean arterial pressure related to a 12% reduction in peripheral resistance
was observed 10 minutes after the priming bolus of ANF. This response was not sustained during the
remainder of the ANF infusion period, nor did it occur in two additional subjects who received ANF
infusions without the priming bolus. Steady state responses consisted of significant reductions in
central venous pressure (15%), stroke volume (13%), and cardiac output (10%), but no reduction in
blood pressure. Plasma norepinephrine levels and peripheral resistance increased (34% and 9%,
respectively) during ANF administration. These data indicate that steady state responses to ANF in
humans consist of decreases in cardiac filling pressures, which reduce cardiac output, unload cardiopulmonary baroreceptors, and activate the sympathetic nervous system. Blood pressure is well
maintained despite striking increases in plasma ANF. (Hypertension 11: 537-544, 1988)
KEY WORDS * atrial natriuretic factor
central venous pressure
blood pressure
A TRIAL natriuretic factor (ANF) is a 28 amino
/ \
acid peptide that circulates in human plasma.'
J . \ . It is synthesized in secretory granules located
primarily within the atrial myocytes2 and is released
from these storage sites during atrial distention. 13
ANF produces diuresis, natriuresis,4 and vasorelaxation. 5 ' 6 In addition, ANF may also inhibit renin, aldosterone, and vasopressin release7"9 and produce intravascular fluid shifts.9-l0
The cardiovascular effects, particularly the hypotension associated with ANF infusions, have been inconsistent in past reports despite the fact that ANF has
• sympathetic nervous system
well-described, potent vasodilatingeffects." Systemic
administration of ANF into humans appears to reduce
blood pressure only when it is given as a bolus 12 ' 13 or
infused in pharmacological doses.14
Several recent studies in anesthetized and conscious
experimental animal preparations indicate that'ANFinduced hypotension may not be due to reductions in
peripheral resistance but is more often associated with
reductions of cardiac output.15"18 In the present study,
we employed several infusion protocols and complete
hemodynamic monitoring to evaluate ANF's cardiovascular effects in human volunteers. Both bolus and
continuous infusions of the 28 amino acid human
ANF-(99-126), which is the primary form of ANF that
circulates in human plasma, were used, while direct
arterial pressure, central venous pressure, and cardiac
output were monitored and plasma norepinephrine levels were determined.
Our data indicate that bolus administration of ANF
produces dynamic responses consisting of transient
hypotension mediated by reductions in peripheral resistance. However, continuous infusions of ANF pro-
From the Departments of Physiology and Anesthesiology, Medical College of Wisconsin and Veterans Administration Medical
Center, Milwaukee, Wisconsin.
Supported by a grant from the American Heart Association,
Wisconsin Affiliate and National Center, and National Heart,
Lung, and Blood Institute Grant HL-29587.
Address for reprints: Thomas J. Ebert, M.D., Ph.D., Anesthesiology Service, 112A, VA Medical Center, 5000 W. National Avenue, Milwaukee, WI 53295-1000.
Received August 7, 1987; accepted January 20, 1988.
537
538
HYPERTENSION
duce steady state effects that include reductions of
cardiac filling pressures, which activate the sympathetic nervous system to maintain blood pressure at
baseline levels.
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Subjects and Methods
Sixteen healthy volunteers, ranging in age from 20
to 28 years, participated in this study after providing
informed written consent. Eight subjects received
ANF infusions, and eight served as time controls and
received isotonic saline. Subjects were randomized to
these groups and not informed of the nature of the
infusate until studies were completed.
Subjects were instructed to eat a morning meal with
no added salt and to abstain from substances containing caffeine, theophylline, and nicotine. Overnight
fluid deficits were replaced with 750 ml of orally administered fluids at breakfast. The subjects took nothing by mouth after this meal and arrived in the laboratory at 0900.
Instrumentation
An 18-gauge catheter was inserted into a peripheral
vein and kept patent by a slow infusion of isotonic
saline at 30 ml/hr. Another catheter was inserted under
sterile conditions into a jugular vein and advanced into
an intrathoracic vein to monitor central venous pressure. A radial artery catheter was inserted for direct
blood pressure measurements and for blood sampling.
Central venous pressure, arterial pressure, and an electrocardiogram were displayed on an oscilloscope.
Digital readings of pressure and heart rate were updated each cardiac cycle.
An impedance cardiograph (Surcom, Minneapolis,
MN, USA) was employed to obtain continuous measurements of stroke volume and cardiac output. This
method has been described and validated in our laboratory and elsewhere.'9"23 Briefly, this method consists
of placement of three circumferential electrodes about
the neck and abdomen and a fourth electrode on the
forehead. A 100-kHz, 4-mA current is transmitted to
the outer two electrodes, and impedance changes within the thorax are detected from the inner two electrodes. Stroke volume is derived from standard calculations.19 A heart sound microphone placed on the
anterior chest wall is employed to aid in the determination of ventricular ejection time.
Absolute stroke volumes derived from impedance
cardiograms compare favorably with those derived
from standard invasive methods. l9 " 23 Most correlations
have been greater than 0.8. Furthermore, our previous
studies20 have demonstrated that this method is exquisitely sensitive to small changes in left ventricular
stroke volume in humans when compared with simultaneous left ventriculograms (r = 0.89). This method
was therefore used to monitor beat-by-beat responses
to ANF infusions.
Systemic vascular resistance was expressed as the
ratio of mean arterial pressure and cardiac output (in
units of dyn-sec-cm" 3 ). Forearm blood flow and distensibility were measured using standard venous oc-
VOL 11, No 6, PART 1, JUNE
1988
clusion plethysmography employing a mercury-in-Silastic, temperature-compensated strain gauge and
saddle placed about the forearm.24 Forearm vascular
resistance was calculated as the ratio of mean arterial
pressure to forearm blood flow. Forearm venous distensibility was calculated from measurements of forearm girth during random intermittent inflations (20,
35, and 50 mm Hg) of a congesting cuff on the upper
arm.
Procedures
Subjects voided and were then instrumented while
supine. Thirty minutes after instrumentation, baseline
hemodynamic recordings were obtained and 50 ml of
arterial blood was withdrawn for determination of
plasma vasopressin, aldosterone, renin activity, catecholamines, ANF, electrolytes, hematocrit, and osmolality. ANF (0.2 mg mixed in 10 ml of preservativefree 0.9 normal saline and filtered through a 0.22-fim
filter) was mixed immediately before each study and
refrigerated. In six volunteers, ANF was given as a
125 ng/kg intravenous bolus and was followed by a
continuous 30-minute infusion at 25 ng/kg/min. In two
additional subjects, the initial priming bolus of ANF
was not given before the 30-minute infusion period.
Equal volumes of isotonic saline were given to eight
volunteers.
Continuous hemodynamic data were recorded on a
strip chart recorder (Model 7, Grass, Quincy, MA,
USA) and simultaneous digital displays were observed. Forearm blood flow was obtained at 30-second
intervals for the first 10 minutes of infusion and during
the 28th to 30th minute of infusion. Blood sampling
was repeated in all subjects after completion of the 30minute infusion period. This procedure was followed
by measurements of forearm distensibility while ANF
infusions continued. Hemodynamic data obtained during the control period and during the 10th and 30th
minute of infusions were statistically analyzed, as
were biochemical data obtained during control and at
30 minutes of infusion. Results were compared with
Student's paired and unpaired t tests and analysis of
variance (ANOVA).
Biochemical Analyses
Plasma arginine vasopressin concentration was determined using antisera and radioimmunoassay procedures described previously." Plasma renin activity
was analyzed by a modification of the method of Sealey and Laragh26 using angiotensin I antisera kindly
provided by Dr. Jean Sealey. Plasma aldosterone was
extracted with dichloromethane and measured using
highly specific antisera (Diagnostic Products, London,
Ontario, Canada)
Norepinephrine was determined from plasma samples that were first adsorbed onto alumina, then eluted,
filtered, and applied to a 5-fim, 4.5 x 250-mm octadecyl reverse-phase column (IBM, Wallingford, CT,
USA), and separated under isocratic conditions using a
0.1 M phosphate buffer containing Na2 EDTA, NaOH,
and Pic B8 (Waters, Milford, MA, USA; pH = 4.8;
539
EFFECTS OF ANF IN HUMANS/Ebert et al.
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0.9 ml/min). The effluent from the column was monitored by an electrochemical detector (Bioanalytical
Systems, West Lafayette, IN, USA) at a potential of
+ 650 mV relative to an Ag/AgCl reference electrode.
The internal standard used was 3,4-dihydroxy-benzylamine (Sigma Chemical, St. Louis, MO, USA). Catecholamines were calculated from the peak heights
using an integrator. The sensitivity of the system was
20 to 25 pg/200 fil injectate, with a 98.5% recovery of
norepinephrine.
Plasma ANF was extracted (1 ml) and reconstituted
for analysis from plasma collected in tubes containing
EDTA, aprotinin, and soybean trypsin inhibitor as described previously.27 The assay procedure was modified for the measurement of ANF in human plasma by
using antisera raised against human ANF-(99-126)
(Peninsula Laboratories, Belmont, CA, USA). The
tracer used was [125I]human ANF-(99-126) obtained
from Amersham (Arlington Heights, IL, USA). Recovery of increasing amounts of this standard added to
human plasma was 82%, while recovery of [123I]ANF
was 92%. The sensitivity of the assay was 3 pg/tube,
and the concentration of peptide that produced 50%
binding was 17 to 20 pg/tube. Interassay and intraassay coefficients of variation averaged less than 10%.
Plasma sodium and potassium were determined using ion sensitive electrodes (Nova-1; Nova Biochemical, Boston, MA, USA). Plasma osmolality was determined using freezing point depression osmometry
(Osmette A; Precision Systems, Boston, MA, USA).
Results
In the present study, eight volunteers received ANF
infusions while eight served as time controls and received isotonic saline infusions. Baseline hemodynamics (Table 1) and plasma levels of ANF, renin
activity, vasopressin, and norepinephrine (Table 2) did
not differ between groups.
Thirty-minute infusions of ANF increased plasma
levels of ANF 8.8-fold, as shown in Table 2. Neither
30-minute ANF nor placebo infusions altered hemato-
TABLE 1. Baseline Cardiovascular Data Obtained from Supine
Volunteers
ANF
Time control
Cardiovascular variable
(n = 8)
(i = 8)
60.1 ±4.7
59.9±3.7
Heart rate (beats/min)
85.5 + 4.3
Stroke volume (ml)
95.2± 10.1
5.4 ±0.4
5.1±0.5
Cardiac output (L/min)
142.5±6.2
143.1
±
2
.
1
Systolic pressure (mm Hg)
73.8±1.6
74.2 + 2.5
Diastolic pressure (mm Hg)
Systemic vascular resis1473.0+121.0 1650.0± 232.0
tance (dyn-sec-cm~5)
Forearm vascular resistance
34.1 ±8.1
(mm Hg-ml~'-min-100 ml) 27.3±6.9
Central venous pressure
7.2±1.0
6.1±0.7
(mm Hg)
Data are means ± SEM.
crit, electrolytes, and osmolality, nor did these infusions influence plasma renin activity, aldosterone, or
vasopressin (see Table 2). There was a significant 34%
increase in plasma norepinephrine during ANF infusions.
Figure 1 demonstrates the progressive reduction in
central venous pressure produced by ANF infusion.
This reduction was significantly different from the
time-control group response within 10 minutes of initiating infusions.
Figure 2 summarizes the 10- and 30-minute responses of the other cardiovascular variables during
infusions. Mean arterial pressure and systemic vascular resistance decreased by 4.8 ± 1.2 mm Hg and
201 ± 60 dyn-sec-cm" 3 respectively, at 10 minutes
into ANF infusions. However, these responses were
not sustained over the remaining 20 minutes of infusion; mean pressure returned to baseline, while systemic vascular resistance was increased significantly
(9%) above baseline. Stroke volume and cardiac output declined by 11.3 ± 4 ml/beat (13%) and 0.5 ±
0.18 L/min (10%) after 30 minutes of ANF infusion.
TABLE 2. Plasma Values from Supine Volunteers
Plasma concentrations
Hematocrit (%)
Sodium (mEq/L)
Potassium (mEq/L)
Osmolarity (mosm/kg)
Renin activity (ng Ang I/ml/hr)
Aldosterone (ng/dl)
Vasopressin (pg/ml)
ANF (pg/ml)
Norepinephrine (pg/ml)
Baseline
Time control
A30 min
ANF
A30 min
Baseline
43.3+1.0
1.6+1.7
39.0+1.7
0.9±0.6
143.5 + 0.6
-2.0±0.8
139.0±1.0
1.1 ±2.2
3.6 + 0.2
3.8±O.l
—0.1 ±0.1
— 0.1 ±0.1
290.2 + 2.0
286.9 ±1.1
-1.0±0.9
-2.8±0.9
1.9±0.6
— 1.1 ±0.4
2.3+0.5
-0.5±0.3
2.6±0.4
3.0 + 0.3
1.0± 1.0
-1.0±0.3
3.5±0.4
3.0+1.0
0.0±0.2
- 0 . 1 ±0.3
37.2 + 4.6
52.8 + 5.5
3.1 ±2.4
466.8 ±54.5*4
107.5±23.0
159.5+19.5
-14.5±5.7
58.7±6.3*4
Data are means ± SEM. A30 min = average change from respective baseline after 30-minute infusions; Ang I :
angiotensin I.
*/><0.05, compared with respective baseline value.
tp<0.05, compared with time control.
HYPERTENSION
540
11, No
6,
PART 1, JUNE
1988
priming bolus of ANF. This similarity consisted of a
30% increase in plasma norepinephrine and a significant increase in peripheral resistance (see Figure 4).
i
A
contra!
venous
VOL
05
0
3TSSSUTS,
mmHg
-O5
*
-1D
.
ANF
.1 S.
0
to
20
Time, mbiutts
30
FIGURE 1. Central venous pressure response to 30-minute infusions of ANF or placebo (time control). Single asterisk indicates response significantly different between groups (p <
0.05). Double asterisk indicates significant reduction from
baseline and significantly different response from that of the
time-control group (p < 0.01).
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Forearm venous distensibility curves are depicted in
Figure 3. These were virtually identical in the two
groups during baseline conditions. ANF infusions resulted in a slight increase and placebo infusions resulted in a slight decrease in forearm distensibility. The
net statistical effect was an apparent augmentation of
forearm distensibility during ANF infusions (p <
0.05).
The cardiovascular responses of two subjects to continuous 30-minute infusions of ANF (25 ng/kg/min)
are shown in Figure 4. In these volunteers, a priming
bolus was not given before initiating infusions and
there were no initial reductions in blood pressure or
peripheral resistance. Steady state responses and plasma ANF levels after 30-minute infusions were similar
to those of the volunteers who had received an initial
Discussion
Studies in experimental animals and the few reports
in humans have revealed inconsistent blood pressure
responses to ANF infusions despite its well-known
potent vasodilating effects."28 In the present study,
we recorded dynamic responses to ANF infusions
when priming boluses preceded infusions. These responses consisted of a transient hypotension mediated
byreductionsin peripheralresistance.However, steady
state effects of ANF appear to activate the sympathetic nervous system (independently of arterial baroreceptorreflexes);plasma norepinephrine and peripheral
resistance were elevated within 30 minutes of infusion.
Theseresponsesmay have been mediated by low-pressure baroreceptor reflexes: ANF reduced cardiac filling pressures, which decreased afferent signals from
cardiopulmonary baroreceptors and elicited reflex in^
creases of sympathetic outflow.
Infusions
In six volunteers, ANF was administered as an initial priming bolus of 125 ng/kg followed immediately
by a continuous infusion at 25 ng/kg/min. This protocol was derived with knowledge of the pharmacokinetic principles of this short-lived peptide. We sought
to initiate immediate elevations of plasma ANF and to
maintain relatively constant levels for 30 minutes by
continuous infusion of this peptide. Steady state plasma levels of ANF after 30 minutes of continuous infu-
bpfn
vucUar
ratatsncs,
ITHTIHQ
mSHnfiOOfnl
FIGURE 2. Response to 30-minute infusions of ANF or placebo (time control). Single (p < 0.05) and double
(p < 0.01) asterisks indicau significantly different effects between groups and significant changes from control.
541
EFFECTS OF ANF IN HUMANS/Ebert et al.
XLTH
FORERRfi
VOLUME.
, PRE-flNF
, PRE-PLflCEBO
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DELTfl
FOREHRN
VOLUME,
DURING RNF
DURING PLflCEBO
of human ANF-(99-126) (100 ng/kg/min; four times
the dose used in the study) into supine volunteers lowered mean blood pressure by 10 mm Hg. This decrease
was associated with significant elevations of plasma
cyclic guanosine 3',5'-monophosphate (which may induce vasodilation). Of interest, 100 ng/kg/min infusions of the synthetic rat (25 amino acid sequence)
ANF peptide did not lower blood pressure in the human volunteers studied by Cody et al.33 Thus, the molecular sequence may be an important parameter in
determining the vascular responsiveness in humans.
In the present study, the reduction in peripheral resistance after bolus administration of ANF was not due
to decreases in forearm resistance. However, potent
forearm vasodilator responses have been demonstrated
when ANF is infused directly into the brachial artery of
humans." Furthermore, continuous incremental systemic infusions of ANF into humans produce progressive increases in forearm skin blood flow.28 We cannot
exclude the possibility that other vascular beds (e.g.,
renal and splanchnic) may have been involved in this
transient reduction in resistance.34"3* Furthermore,
pathophysiological boluses of ANF into humans may
RESPONSE TO f*f
18
38
30
48
58
60
VENOUS OCCLUSION PRESSURE.
hEKHT
RflTE. 55
FIGURE 3. Forearm distensibility curves were virtually identical between groups at baseline (top graph) but were significantly greater fp < 0.05, by ANOVA) after 30 minutes of ANF
infusions compared with the time-control (placebo) group (bottom graph).
sion of ANF were 519 ± 56 pg/ml. This value is an
eightfold increase from basal levels and is similar to
that seen in pathophysiological states such as congestive heart failure, renal failure, and severe liver cirrhosis.29"32 Similar plasma levels of ANF were attained
without a priming dose of ANF in two subjects. However, these levels likely were established more gradually than in those receiving priming boluses of ANF.
Early Transient Responses to ANF
Ten minutes ( ± 0 . 6 minute) after initiating infusions with a priming bolus of 125 ng/kg, arterial pressure had declined to its minimum. Significant reductions of systolic (3%), diastolic (7%), and mean
pressure (5%) occurred. This response was secondary
to a decrease in systemic vascular resistance. Forearm
vascular resistance tended to decline as well, but this
response was not significant. Continuous infusions of
ANF that were not preceded by a priming bolus did not
elicit hypotension or reduce peripheral resistance.
These findings suggest that the blood pressure-lowering effect of ANF is dependent on either the rate of
change in plasma ANF levels or the absolute plasma
concentration of this peptide (or both). Support for the
latter possibility is derived from the data of Ohashi et
al.14: Continuous infusions (without a priming bolus)
25 n g A g / « i n
— SiDJect BfKB
— S i i d e c t CSH5
05
110
STROKE
VOLUME,90
70
MOW H
PRTERIflL
PRESSURE,
90
2000
1600
CENTRRL
VENOUS
PRESSURE,
Central
10
TIME, B i n
30
FIGURE 4. Cardiovascular responses of two subjects to 30minute infusions of ANF (25 ng/kg/min). These infusions were
initiated^ without a priming bolus. TPR = total peripheral resistance.
542
HYPERTENSION
have transiently reduced sympathetic neural outflow
and vascular resistance, thereby promoting an initial
hypotension.37
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Steady State Effects of ANF
The initial decreases in systemic vascular resistance and blood pressure produced by ANF were not
sustained despite continuous infusions of the peptide.
The major effects of steady state infusions of ANF
(either with or without the priming bolus) were on
central venous pressure and cardiac output. Central
venous pressure declined progressively (to 15% below
baseline) during each 30-minute infusion period. Several earlier studies in conscious experimental animals16"18 and humans33 also demonstrated reductions in
central venous pressure, right atrial pressure, and pulmonary capillary wedge pressure during ANF infusions.
These reductions in cardiac filling pressures may
have been due to increases in venous capacitance or to
enhanced renal excretion of fluid volume. However,
support for these two possibilities is weak, since ANF
is not a powerful venodilator6 and ANF infusions provoke marked reductions in circulating blood volume in
anephric animals. 38 ' 39 A more likely explanation for
the consistent reductions in central venous pressure
noted during ANF infusions is that intravascular fluids
shift to extravascular sites through alterations in Starling forces (particularly hydraulic conductivity) within
the capillary beds.40'*1 In the present study, measurements of forearm volume changes during venous occlusion revealed greater volume increases during ANF
infusions. This effect may be due to compliance or
permeability changes in the forearm. If this isolated
response occurs throughout the entire vascular tree, it
is not difficult to reconcile the significant reductions in
central venous pressure produced by ANF.
The reduction in cardiac output noted during ANF
infusions has been an inconsistent finding in previous
reports. This response has been demonstrated in several conscious animal preparations,15"18 while studies in
humans33 have failed to demonstrate such an effect.
None of these reports employed the 28 amino acid
peptide, human ANF-(99-126), which is the primary
circulating form of this peptide in human plasma.1
Other ANF analogues may have subtle differences in
biological activities. 4243 Our findings of reduced
stroke volume and cardiac output during ANF infusions are strengthened by the demonstration of the
absence of change in these parameters in the timecontrol population. The reductions in stroke volume
and cardiac output during ANF infusions are most likely due to Frank-Starling mechanisms involved by reductions in cardiac filling pressures, since ANF does
not appear to reduce cardiac inotropy directly.44
Sympathetic Nervous System Activation
We were unable to demonstrate a sustained reduction in blood pressure or peripheral resistance in human volunteers receiving ANF infusions, despite the
VOL 11, No
6, PART 1, JUNE
1988
well-described vascular smooth muscle relaxing effect
of this peptide. In contrast, ANF infusions resulted in
an elevation of peripheral resistance. Several recent
studies in conscious rats, sheep, and dogs have also
demonstrated that peripheral resistance does not decrease and may increase markedly during ANF infusions.15"18 We believe this response is predictable
based on our understanding of cardiopulmonary baroreceptor physiology. ANF-induced reductions in central venous pressure unload low pressure cardiopulmonary baroreceptors and elicit vasoconstriction. 4546
In support of this explanation (i.e., a reflex neural
mechanism eliciting resistance increases), we and others 1 0 4 7 4 8 have documented elevations of plasma norepinephrine during ANF infusions. These elevations in
norepinephrine do not appear to be related to arterial
baroreceptor reflex activation in response to the initial
transient drop in blood pressure produced by ANF
because plasma norepinephrine increased similarly
during infusions of ANF that were not preceded by
boluses and therefore did not provoke hypotension.
We reason that reductions in central venous pressure
did not elicit significantly measurable reflex forearm
vasoconstriction in the present study because direct
vascular effects of ANF that increase forearm skin and
muscle blood flow1128 may have offset measurable
reflex increases in forearm vascular resistance.
Hormonal Responses to ANF Infusions
We were unable to demonstrate significant reductions in renin, aldosterone, and vasopressin in our investigation despite in vitro evidence that ANF inhibits
the release of these hormones. 7 ' 8 We speculate that the
pronounced reductions in central venous pressure produced by ANF in the present study may have offset
potential ANF-induced reductions in these hormones.
Furthermore, the short infusion protocol, which was
sufficient to demonstrate profound cardiovascular effects of ANF, may have been insufficient to provoke
more gradual hormonal responses. Larger doses of
ANF infused into seated or salt-depleted human volunteers over longer periods appear to reduce plasma concentrations of these hormones. 3314748
Our results indicate that infusions of human ANF(99-126) that produce pathophysiological elevations
of plasma ANF do not produce sustained reductions in
blood pressure in humans. A 125 ng/kg priming bolus
of human ANF-(99-126) provoked only transient reductions in peripheral resistance and blood pressure.
These responses were not sustained during continuous
infusions of this peptide, nor did they occur in subjects
who received continuous infusions of ANF without a
preceding bolus. Steady state responses to ANF infusions of 25 ng/kg/min consisted of reductions in cardiac filling pressures and concomitant declines in stroke
volume and cardiac output. These responses produced
reductions of cardiopulmonary baroreceptor stimulation, which elicited reflex sympathetic nervous system
activation; peripheral resistance and plasma norepinephrine levels were elevated above baseline levels
during steady state elevations of ANF.
EFFECTS OF ANF IN HUMANS/Ebert et al.
Acknowledgments
The authors thank Kelly Zanoni and Stella Chiu for their careful
measurement of plasma hormones in this study.
24.
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25.
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VOL 11, No 6, PART 1, JUNE 1988
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Dynamic cardiovascular responses to infusions of atrial natriuretic factor in humans.
T J Ebert, M M Skelton and A W Cowley, Jr
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Hypertension. 1988;11:537-544
doi: 10.1161/01.HYP.11.6.537
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