Vol. 282, Issue 5, R1468-R1476, May 2002
Frequency modulation of mesenteric and renal vascular
resistance
Olaf
Grisk1 and
Harald M.
Stauss2
1 Institut für Physiologie,
Ernst-Moritz-Arndt-Universität Greifswald, 17495 Karlsburg;
and 2 Johannes-Müller-Institut für
Physiologie, Humboldt-Universität zu Berlin (Charité),
10117 Berlin, Germany
 |
ABSTRACT |
The hypothesis was
tested that low-frequency vasomotions in individual vascular beds
are integrated by the cardiovascular system, such that new
fluctuations at additional frequencies occur in arterial blood
pressure. In anesthetized rats (n = 8), the sympathetic
splanchnic and renal nerves were simultaneously stimulated at
combinations of frequencies ranging from 0.075 to 0.8 Hz. Blood pressure was recorded together with mesenteric and renal blood flow
velocities. Dual nerve stimulation at low frequencies (<0.6 Hz) caused
corresponding oscillations in vascular resistance and blood pressure,
whereas higher stimulation frequencies increased the mean levels. Blood
pressure oscillations were only detected at the individual stimulation
frequencies and their harmonics. The strongest periodic responses in
vascular resistance were found at 0.40 ± 0.02 Hz in the
mesenteric and at 0.32 ± 0.03 Hz (P < 0.05) in
the renal vascular bed. Thus frequency modulation of low-frequency
vasomotions in individual vascular beds does not cause significant
blood pressure oscillations at additional frequencies. Furthermore, our
data suggest that sympathetic modulation of mesenteric vascular
resistance can initiate blood pressure oscillations at slightly higher
frequencies than sympathetic modulation of renal vascular resistance.
rats; sympathetic nervous system; arterial blood pressure; blood
pressure variability; Mayer waves
| |
INTRODUCTION |
BLOOD
PRESSURE (BP) variability has been identified as an independent
risk factor for cardiovascular morbidity and mortality (13,
17). In addition, a well-regulated perfusion pressure is a
necessity for proper organ function. Thus the body is equipped with a
variety of mechanisms aimed at stabilizing arterial BP. A major
component of short-term BP regulation is mediated through the
sympathetic nervous system. Because perfusion of peripheral organs
needs to be adjusted according to the individual requirements, it is
not surprising that sympathetic outflow to the peripheral effector
organs is not uniform (1, 5, 19). Instead, it is
individually adjusted to maintain whole body homeostasis. Thus sympathetic discharge patterns may differ regionally. Major inputs to
the sympathetic nervous system originate from the arterial baroreceptors. These inputs modulate sympathetic outflow to the periphery to adjust vascular tone and, thereby, maintain BP at a
constant level. It has been shown that this baroreceptor reflex has the
potential to generate self-sustained oscillations at 0.4 Hz in rats
(3). These oscillations were indeed identified in peripheral sympathetic nerve activity (20), vascular
conductances (12), total peripheral resistance
(10), and arterial BP (10-12, 20).
The resonance frequency of the baroreceptor reflex at 0.4 Hz in rats
(3) results from the time lag at the site of the vascular neuroeffector junction. Due to this time lag, sympathetic modulation of
vascular resistance is limited to frequencies <0.1 Hz in humans (21) and 0.6 Hz in rats (22). These corner
frequencies were derived from studies based on sympathetic nerve
stimulation and concomitant recordings of local blood flow and arterial
BP. The conclusion was that sympathetic-mediated vasomotions and
consecutive BP fluctuations are limited to low frequencies (14,
16, 21, 22, 24, 25). However, it has also been reasoned that in multibranched microvascular networks a contracting mechanism may induce different oscillatory patterns, including periodic,
quasiperiodic, and chaotic fluctuations (28). Thus one may
speculate that vasomotions in individual vascular beds can be
integrated in such a way that new fluctuations in total peripheral
vascular conductance and, hence, in arterial BP occur at additional
frequencies. Theoretically, such a phenomenon is possible by
"frequency mixing" of local oscillations in the vessel diameter and
vascular conductance. An example is given in Fig.
1, which illustrates the following
mathematical considerations. The whole body circulation is arranged as
parallel circuits. Therefore, arterial BP depends on cardiac output
(CO) and the individual vascular conductances (Ci) in the
following manner
|
(1)
|
The changes in the radii of the vessels
(ri) in response to periodic sympathetic
stimulation may be approximated by sine waves, such as
ri = ai × sin (
i) + mi. The parameter
ai represents the amplitude, i the
frequency, and mi the aperiodic component of the radius
(i.e., the mean of the radius). According to Hagen-Poiseuille's law,
individual conductances can be estimated as (l, length of the vessel; 
, blood viscosity, f = 
/(8 × l × )
![C<SUB>i</SUB><IT>=</IT><FR><NU>&pgr;r<SUP>4</SUP><SUB>i</SUB></NU><DE>8<IT>l&eegr;</IT></DE></FR><IT>=f × </IT>[a<SUB>i</SUB> × sin (&ohgr;<SUB>i</SUB>)<IT>+</IT>m<SUB>i</SUB>]<SUP>4</SUP>](/content/vol282/issue5/fulltext/R1468/img002.gif)
|
(2)
|
If only two peripheral vascular beds (with equal length
l) are considered, arterial BP can be calculated as
|
(3)
|
In Fig. 1, Eq. 3 was used to model a circulatory system
with constant flow (representing CO in the whole body circulation) and
two parallel circuits of similar vessel length. The length (l) of the vessels was set to 5 mm, the mean radii
(m1 and m2) of the vessels were set to 100 µm
and 150 µm, respectively, the viscosity () was set to 2.8 mPa · s, and the flow (CO) to 15 ml/min. The frequencies (i)
for the periodic changes in the radii of both vessels were 0.3 and 0.5 Hz. From top to bottom, the amplitudes (ai) of the changes
in the vessel radii were lowered subsequently. This model indeed
reveals that the phenomenon of frequency mixing occurs. In addition to
the peaks at 0.3 and 0.5 Hz, the BP power spectrum reveals additional
peaks at the frequencies of the sum (0.8 Hz) and the difference (0.2 Hz) of the individual stimulation frequencies. It is worthwhile to note
that the phenomenon of frequency mixing also occurs if the frequencies
present in sympathetic nerve activity to individual target organs that
are important in giving rise of the oscillation in BP are similar
(i.e., = 1 = 2). In this
case, the mixing product at 1 
2
would not be present, but a mixing product at two times the stimulation
frequency (1 + 2 = 2 × )
would appear.
View larger version (49K):
[in this window]
[in a new window]
|
Fig. 1.
Illustration of the phenomenon of "frequency mixing."
The effects of periodic changes in the radii of two vessels on arterial
blood pressure (BP) and its power spectrum are calculated according to
Eq. 3 given in the introduction. From top to
bottom, the amplitudes of the periodic changes in the radii
of the vessels are reduced continuously. The frequencies
(i) of the oscillations in vessel diameter are 0.5 and
0.3 Hz, respectively. Only when the amplitudes of the changes in vessel
radii are large, prominent "mixing products" are found at 0.2 and
0.8 Hz in the blood pressure power spectra.
|
|
The aim of the present study was to investigate if frequency mixing of
vascular conductance occurs, such that periodic sympathetic stimulation
of two distinct vascular beds causes oscillations of total peripheral
conductance and, hence, arterial BP at the individual stimulation
frequencies and at the sum and difference of both stimulation
frequencies. If this hypothesis is true, sympathetically mediated BP
oscillations can occur at frequencies higher than the highest frequency
that can be transmitted from sympathetic nerves to vascular smooth
muscles. As an experimental approach, sympathetic nerves to distinct
vascular beds (splanchnic and renal nerves) were stimulated with
combinations of different stimulation frequencies and blood flow
velocities in the mesenteric and renal vascular beds were recorded
together with arterial BP. In addition to the investigation of the
frequency mixing of vascular conductance, this approach also allowed us
to compare the frequency response characteristics of sympathetic
modulation of vascular tone in the mesenteric and renal circulations
within the same animal.
| |
METHODS |
Animals and surgical procedures.
Experiments were performed in eight 11-wk-old anesthetized
Sprague-Dawley rats (Charles River, Sulzfeld, Germany) weighing 378.5 ± 3.3 g. The study was approved by federal authorities
and fully conforms with the "Guiding Principles for Research
Involving Animals and Human Beings" of the American Physiological Society.
Anesthesia was initiated by an intraperitoneal dose of 60 mg/kg body wt
pentobarbital sodium (provided by the pharmacy of the Charité
Hospital, Berlin, Germany). Animals were placed on a heating pad to
maintain body core temperature at 38°C and breathed spontaneously.
Catheters were implanted into the right femoral artery and vein and an
intravenous infusion of isotonic saline (1.0 ml/h) was started to
compensate for consecutive fluid losses. The superior mesenteric and
the left renal artery were approached via a left flank incision and
ultrasound Doppler flow probes (DBF-120A, 20 MHz, Hugo Sachs
Elektronik) were implanted around both vessels (22). Care
was taken not to damage nerves running along the respective arteries.
The major splanchnic and left renal nerves were identified, dissected
free from surrounding tissue, and placed on bipolar electrodes
(36-gauge stainless steel, Cooner Wire, Chatsworth, CA) (7,
8). Several branches of the renal nerve were stimulated through
the electrode, and the one giving the strongest renal vasoconstriction
was selected for the experiments. To avoid afferent nerve stimulation,
both nerves were squeezed with a pair of tweezers and tightly ligated
(9-0 suture material, Ethilon, Ethicon, Norderstedt, Germany)
proximal to the electrode. Finally, the nerve-electrode preparations
were electrically insulated with silicon gel (Silgel 604A and 604B,
Wacker-Chemie, Munich, Germany).
Hemodynamic recordings and nerve stimulation.
The arterial BP signal was provided by an Isotec pressure transducer
connected to a direct current bridge amplifier (both Hugo Sachs
Elektronik). Heart rate was calculated online from the arterial BP
signal. Mesenteric and renal blood flow velocity signals were obtained
from a multichannel pulsed ultrasound Doppler device (model PD 20, Crystal Biotech, Hopkinton, MA). These hemodynamic signals together
with the trigger signals from the nerve stimulator unit were digitized
with a sampling rate of 500 Hz and recorded on a Linux workstation by a
freely available data-acquisition software (XmAD,
ftp://sunsite.unc.edu/pub/Linux/science/lab).
Dual nerve stimulation was accomplished via a computer-controlled
two-channel nerve stimulator unit (developed at the
Johannes-Müller-Institut für Physiologie,
Humboldt-University, Berlin, Germany). With this unit, trains of
rectangular impulses (impulse frequency 20 Hz, impulse duration 2 ms,
train duration 500 ms) were applied to the major splanchnic and renal
nerves at different combinations of stimulation frequencies. The
stimulation voltage was individually adjusted for both nerves to obtain
noticeable mesenteric and renal blood flow reduction with the least
voltage. Typically, the stimulation voltage was 2.0 V.
Experimental protocol.
The experimental protocol was performed in anesthetized rats and
consisted of eight stimulation sequences (5 min duration each) preceded
by individual baseline recordings (5 min). Anesthesia was maintained by
intravenous bolus injections of 10 mg/kg body wt pentobarbital sodium
as needed. After each anesthetic dose, the recording was stopped until
stable baseline conditions were reestablished and the protocol was
continued with the baseline recording for the next stimulation
sequence. Eight combinations of stimulation frequencies for the major
splanchnic and renal nerves were applied in a randomized order
(Table 1).
Data analysis.
For each rat (n = 8), eight stimulation sequences and
eight respective baseline recordings were obtained. In each of these 128 data files, the signals for arterial BP, mesenteric and renal blood
flow velocity, and the trigger signals from the stimulator were stored
at a sampling rate of 500 Hz. Systolic, mean, and diastolic BP as well
as heart rate were calculated on a beat-by-beat basis. Similarly, for
each pulse wave, the areas under the curve of the mesenteric and renal
blood flow velocity signals were calculated and served as mean blood
flow velocity signals (kHz Doppler shift). Mesenteric and renal
vascular resistance were calculated for each heart beat as the ratio of
mean arterial BP and mean blood flow velocity. Then, all signals were
low-pass filtered with a corner frequency of 5 Hz (4th-order
Butterworth filter) and resampled at 15 Hz, resulting in equally spaced
time series. From these signals 4,096 data values (274 s) were selected
for further analysis based on the stationarity of the signals.
Stable baseline conditions throughout the experimental protocol were
confirmed by comparing the hemodynamic parameters during the eight
individual baseline recordings. The hemodynamic effects of the nerve
stimulation are given as the absolute differences from baseline for
mean BP and heart rate and as percent changes from baseline for
mesenteric and renal blood flow velocities and the respective vascular resistances.
Sympathetic transmission to the mesenteric and renal vasculature was
investigated by transfer function analysis. First, the power spectra
for mesenteric and renal vascular resistance were calculated by the
fast Fourier transform (FFT, 4,096 values) and the areas under the
curve in frequency bands of ±0.015 Hz around each individual
stimulation frequency were determined. The relative spectral power was
obtained by the ratio of this area to the area under the total power
spectrum from 0.0 to 5.0 Hz and was expressed as percent changes from
the relative spectral power of the preceding baseline recording. In
each rat, these percent changes in spectral power were fitted to a
damped oscillator model as described previously (4, 25).
The model was
In this model, X(f) is the
system output, a is the amplitude of the driving force of the
oscillator, b is the resonance frequency, and c is a damping parameter.
Therefore, calculation of the parameter b allows estimation of the
frequency at which periodic oscillations in sympathetic tone are most
effectively translated into corresponding oscillations of vascular
resistance. Second, the squared coherence function as well as the gain
and phase angle of the transfer function between the marker signals
from the stimulator (input signal) and mesenteric and renal vascular
resistance (output signal) were calculated. Therefore, using the FFT
algorithm, autospectral density functions were determined from the
15-Hz time series of the marker signals (input function
Sxx(q)) and the vascular resistance signals (output
function Syy(q)), together with the cross-spectrum
(Sxy(q)) of both signals. The autospectral density
functions and the cross-spectrum were then subjected to a moving
average process with a window size of 11 values, corresponding to
0.7 s. This step was necessary to prevent coherence from being unity.
The squared coherence function 
2(q) permits
identification of frequency bands in which the input and output signals
are associated with each other and was calculated using the relation
The gain of the transfer function |H(q)| provides
information on how strongly the input signal alters the output signal
and was derived from the relation
The phase angle 
(q) is a measure of the time delay between
both signals and was calculated from the real part HR(q)
and the imaginary part HI(q) of the complex transfer
function H(q) according to
For each rat, the phase angles for the individual stimulation
frequencies were fitted to a linear regression line. The frequency at
which this line had a phase angle of radiant was determined. At
this frequency the input (stimulation) and output (vascular resistance)
signals are out of phase, i.e., the stimulation and the vascular
resistance vary in opposite directions.
The effects of dual nerve stimulation on arterial BP oscillations were
investigated by calculating the power spectra from the mean BP signals.
The areas under the curve of the power spectra were determined in
frequency bands of ±0.015 Hz around the splanchnic nerve stimulation
frequencies, the renal nerve stimulation frequencies, the sums of
splanchnic and renal nerve stimulation frequencies, and the absolute
differences of the splanchnic and renal nerve stimulation frequencies
(see Table 1). Finally, the differences of these areas under the curve obtained from the recordings during stimulation and baseline conditions were calculated.
Statistics.
All data are presented as means ± SE. Statistical comparisons
between baseline conditions and stimulation were done by paired Student's t-test. Comparisons between the mesenteric and
the renal vascular beds were done by unpaired Student's
t-test. Comparisons between parameters at different
stimulation frequencies were done by one-way analysis of variance for
repeated measures and post hoc Newman-Keuls tests.
| |
RESULTS |
Hemodynamic effects of dual nerve stimulation.
The baseline values obtained during the control recordings that
preceded each stimulation sequence are provided in Fig.
2. Stable baseline conditions were
obtained for all hemodynamic parameters throughout the experimental
protocol. An original recording during dual nerve stimulation is shown
in Fig. 3. As demonstrated in this
example, mesenteric and renal blood flow velocity independently oscillated in response to the splanchnic and renal nerve
stimulation, respectively. As the stimulation frequencies
increased, the amplitude of these oscillations vanished and tonic
hemodynamic responses were obtained (Fig.
4). Vascular resistance in the mesenteric and renal vascular beds gradually increased, whereas the
corresponding blood flow velocities decreased. Consequently,
hypertensive and bradycardic responses were obtained
for arterial BP and heart rate.
View larger version (28K):
[in this window]
[in a new window]
|
Fig. 2.
Baseline values obtained during the control recordings
that preceded each stimulation sequence. Stable baseline conditions
were obtained throughout the experimental protocol. BP, systolic, mean,
and diastolic blood pressure; HR, heart rate; MBF, mesenteric blood
flow velocity; RBF, renal blood flow velocity; MR, mesenteric vascular
resistance; RR, renal vascular resistance. The x-axis refers
to the stimulation sequences given in Table 1. bpm, Beats/min.
|
|
View larger version (41K):
[in this window]
[in a new window]
|
Fig. 3.
Original recording during dual nerve stimulation at
frequencies of 0.075 Hz (splanchnic nerve) and 0.2 Hz (renal nerve).
From top to bottom: BP, HR, MBF, and RBF. The
markers for splanchnic and renal nerve stimulation are added below the
respective flow signals.
|
|
View larger version (34K):
[in this window]
[in a new window]
|
Fig. 4.
Changes ( ) in hemodynamic parameters during dual nerve
stimulation. Absolute changes are given for mean arterial blood
pressure (MAP) and HR. Percent changes are provided for MBF and RBF and
the respective vascular resistances (MR, RR). * P < 0.05 values during dual nerve stimulation compared with the respective
baseline values. The x-axis refers to the stimulation
sequences given in Table 1.
|
|
Sympathetic transmission to the vasculature.
Sympathetic transmission to the mesenteric and renal vasculature were
investigated by transfer function analysis (Fig.
5). In both vascular beds, sympathetic
nerve stimulation caused marked increases in spectral power at
stimulation frequencies between 0.2 and 0.6 Hz. The strongest responses
were found at 0.40 ± 0.02 Hz for mesenteric vascular resistance
and at 0.32 ± 0.03 Hz (P < 0.05) for renal
vascular resistance (resonance frequencies of the damped oscillator
model). A second maximum of less intensity was found in the renal
vascular response to periodic stimulation at frequencies between 0.5 and 0.6 Hz (mean frequency 0.52 ± 0.03 Hz). For all stimulation
frequencies, the squared coherence (2(q)) between the
marker signals of the stimulator and vascular resistance was above 0.8 and 0.6 for the mesenteric and renal vascular beds, respectively. In
both vasculatures, the gain of the transfer function (H(q)) was large
for all stimulation frequencies below 0.5 Hz and gradually declined at
higher stimulation rates. The phase angle ((q)) was close to zero at
low stimulation frequencies (i.e., stimulation was almost in phase with
vascular resistance) and linearly decreased with increasing stimulation
frequencies. The oscillations in mesenteric resistance were out of
phase with the stimulation (i.e., the phase was radiant) at
0.55 ± 0.01 Hz, whereas renal resistance was out of phase with
the stimulation at 0.47 ± 0.02 Hz (P < 0.05).
View larger version (25K):
[in this window]
[in a new window]
|
Fig. 5.
Transfer function analysis between the marker signals
from the stimulator and mesenteric (left) and renal
(right) vascular resistance. Top: percent changes
from baseline in spectral power. The circles represent the resonance
frequencies of the damped oscillator model. * P < 0.05 values during dual nerve stimulation compared with the respective
baseline values. Middle: gain of the transfer function.
* P < 0.05 vs. stimulation at 0.8 Hz.
Bottom: phase angles between the marker signal and vascular
resistance. The circles indicate the frequencies at which vascular
resistances are out of phase with the stimulation.
|
|
Frequency modulation of vascular resistance.
To investigate if frequency mixing occurs in the circulation,
such that new mixing products occur at additional frequencies, the
power spectra of mean BP were calculated during dual nerve stimulation
(Fig. 6). These spectra revealed clearly
detectable peaks at the frequencies of splanchnic and renal nerve
stimulation, but not at the "mixing frequencies," i.e., the sums
and absolute differences of both stimulation frequencies. Only when the
stimulation frequencies were 0.2 and 0.3 Hz or 0.6 and 0.4 Hz for the
splanchnic and renal nerves, respectively, were peaks detected at the
absolute difference of the stimulation frequencies (i.e., at 0.1 or 0.2 Hz). However, in these cases, the absolute differences are equal to
one-half of one of the stimulation frequencies and, therefore, may be
considered to be harmonics and not to be elicited by frequency mixing.
View larger version (22K):
[in this window]
[in a new window]
|
Fig. 6.
Power spectra calculated from MAP during the 8 stimulation
sequences. The splanchnic and renal nerve stimulation frequencies are
given on the left and right axis, respectively.
The bottom (x-axis) represents the response
frequency on a logarithmic scale. Responses are found at stimulation
frequencies up to 0.6 Hz.
|
|
The quantitative analysis is shown in Fig.
7. There were strong responses in
arterial BP at stimulation frequencies up to 0.4 Hz for splanchnic and
up to 0.3 Hz for renal nerve stimulation, again indicating that
sympathetic transmission to the renal vasculature is more sluggish than
that to the mesenteric circulation. However, at the mixing frequencies
(sums and absolute differences of the splanchnic and renal stimulation
frequencies), no considerable responses were found in the power spectra
of mean BP. Thus frequency mixing within the circulation does not seem
to initiate oscillations in arterial BP at additional frequencies.
View larger version (21K):
[in this window]
[in a new window]
|
Fig. 7.
Power spectral analysis of MAP during dual nerve stimulation.
Left: changes in spectral power from baseline at the
frequencies of splanchnic (top) and renal nerve stimulation
(bottom). Right: changes in spectral power from
baseline at the frequencies of the sums (top) and absolute
differences (bottom) of the splanchnic and renal nerve
stimulation frequencies. * P < 0.05 values during
dual nerve stimulation compared with the respective baseline
values.
|
|
| |
DISCUSSION |
There are two major findings in this study. First, in
contrast to theoretical considerations, vasomotions in local vascular beds are not integrated in a way such that new fluctuations at additional frequencies occur in arterial BP. Second, the frequency response characteristics of sympathetic transmission (including release
of the neurotransmitter, postjunctional signal transduction, and
interaction of the contractile filaments) to the renal vascular bed
differ from that to the mesenteric circulation. Sympathetic modulation
of mesenteric vascular resistance can initiate BP oscillations at
higher frequencies than sympathetic modulation of renal vascular resistance.
Local vasomotions can have a large impact on BP variability. The
underlying mechanisms involve local changes in vascular conductance that are translated into corresponding fluctuations in total peripheral resistance, which, in turn, lead to increased BP variability. As
outlined in the introduction, these integrative properties of the
cardiovascular system may theoretically generate BP oscillations at the
frequencies of the sum and the difference of the frequencies of the
local vasomotions. Using dual nerve stimulation, we were able to induce
independent oscillations in vascular conductance in the renal and
mesenteric vascular beds. However, in contrast to theory, we
could not detect BP oscillations at frequencies other than those of the
individual stimulation frequencies and their harmonics. A closer look
at Fig. 1 may explain the lack of the "mixing products" in the BP
power spectra. With decreasing amplitudes of the oscillations in vessel
radius (from top to bottom), the mixing products become continuously
smaller. Mathematically, this relationship between the amplitudes of
the oscillations in vessel radius and the size of the mixing products
in arterial BP can be investigated more easily by considering
oscillatory changes in vascular resistance instead of dealing with
oscillatory changes in vessel diameter.
|
(4)
|
|
(5)
|
|
(6)
|
According to Eq. 6 the amplitudes of
total peripheral resistance oscillations that result from independent
oscillations in vascular resistance in two distinct vascular beds can
be estimated from the numerator. The amplitudes of the oscillations in
total peripheral resistance (RT) at the stimulation
frequencies depend on the product of the amplitude of the oscillation
in one local vascular resistance and the aperiodic component (mean
level) of the other (a1m2 or
a2m1). In contrast, the amplitude of the
oscillation at the frequency of the sum and difference of the
individual stimulation frequencies is equal to one-half of the product
of the amplitudes of the oscillations in both local circulations
(a1a2/2). However, these amplitudes
(factors a1 and a2) are typically small
compared with the aperiodic component (mean level, factors
m1 and m2) of local vascular resistance.
Therefore, potential oscillations in total peripheral resistance at the
sum and the difference of the respective stimulation frequencies would
consist of even smaller amplitudes. Thus the impact of the latter
oscillations on systemic arterial BP might not have been big enough to
induce detectable BP oscillations under our experimental conditions.
The frequency response characteristics of sympathetic transmission to
the vasculature has been studied for the mesenteric (22),
iliac (2), and cutaneous circulation (25) in
the rat and for the renal vascular bed in rabbits (9, 14,
16). In these studies sympathetic nerves were electrically
stimulated with different stimulation frequencies and the responses in
local vascular resistance or conductance were determined. In the rat, sympathetic neuroeffector junction allowed transmission of higher frequencies in the mesenteric circulation (up to 0.5 Hz) than in the
iliac vascular bed (0.13 Hz) or the skin (up to 0.1 Hz). The renal
vasculature in the rabbit responded most effectively to sympathetic
stimulation frequencies below 0.4 Hz. However, due to species
differences, it may not be valid to compare the frequency response
characteristics obtained in rats and rabbits. In rats, only indirect
evidence for the frequency response characteristic of sympathetic
modulation of renal blood flow is available. In a study, initially not
designed to characterize the frequency response, transfer function
analysis of renal sympathetic nerve activity and renal blood flow
during thermal and somatosensory stimulation (6) revealed
a high gain of the transfer function between nerve activity and blood
flow between 0.3 and 0.4 Hz. Using dual nerve stimulation and
simultaneous recordings of regional blood flows, we were able to
directly compare the frequency response characteristics of sympathetic
transmission to the mesenteric and renal vasculature within the same
animal. By this approach, we could confirm the frequency range of
sympathetic modulation of renal vascular tone suggested by DiBona and
Sawin (6). In addition, the results of this study suggest
that the frequency of sympathetically mediated BP oscillations can be
slightly higher if induced via the mesenteric (up to 0.4 Hz) compared
with the renal circulation (up to 0.3 Hz).
The frequency response characteristic of the renal vasculature revealed
two distinct maxima at 0.32 ± 0.03 and at 0.52 ± 0.03 Hz.
Although the intensity of the renal vascular response at the lower
frequency (0.32 Hz) was large enough to initiate corresponding BP
oscillations, the response at the second maximum (0.52 Hz) was not
transferred to arterial BP. Thus with regard to the frequency of Mayer
waves, fluctuations in renal vascular resistance are only relevant at
frequencies below 0.4 Hz. In addition, it should be noted that the
intensity of the stimulation in our study was not adjusted to the
decreasing cycle length at increasing stimulation frequencies. Thus
relative to the cycle length, the stimulation intensity was larger at
higher stimulation frequencies. Therefore, we cannot totally exclude
the possibility that the second maximum in the spectral response of the
renal vascular bed shown in Fig. 5 (top) is due to the
larger relative stimulation intensity at 0.6 Hz compared with 0.5 Hz.
However, if the second maximum were only due to the larger relative
stimulation intensity, one would expect a similar second maximum in the
mesenteric circulation, where we found only one maximum at a
stimulation frequency of 0.4 Hz. It is, however, interesting to note,
that a similar bimodal distribution for the frequency response
characteristic of the renal vasculature has been described in rabbits
(14). Probably due to species differences, the response
frequencies were lower than those in the rat (0.12 and 0.32 Hz). In
this study (14) the frequency response characteristic of
the renal vasculature to periodic sympathetic nerve stimulation was
differentiated for the medullary and cortical blood flow using the
laser-Doppler technique. The bimodal distribution of the frequency
response was identified in total renal blood flow (transit time flow
probe) and in the laser-Doppler flux signal of the renal medulla, but not in that of the cortex. Therefore, the authors suggested that the
renal cortex determines the mean level of renal vascular resistance, whereas the medulla is specifically important for the periodic component. This assumption is also supported by the finding that reflex increases in renal sympathetic tone specifically induced renal cortical vasoconstriction without affecting medullary blood flow
(15).
In conclusion, this study demonstrates that local vasomotions in
individual vascular beds are not integrated by the overall cardiovascular system, such that new fluctuations at additional frequencies occur in arterial BP. In addition, our results, obtained by
a dual nerve stimulation technique, suggest that periodic sympathetic modulation of mesenteric vascular resistance can initiate slightly higher frequency oscillations of arterial BP than periodic sympathetic modulation of renal vascular resistance.
Perspectives
The significance of the frequency response characteristics of
individual vascular beds to sympathetic inputs is that these vascular
responses are translated into oscillations of total peripheral resistance and arterial BP. The corresponding oscillations in arterial
BP are the so-called Mayer waves (18). In rats, the Mayer
waves are located between 0.2 and 0.6 Hz with a mean frequency at 0.4 Hz. Because the optimum of sympathetic transmission to the vasculature
differs in individual local circulations, one may assume that the
frequency of the Mayer waves reflects an average of the frequency
response characteristics of all local circulations. In this averaging
process, organs such as the kidneys that receive a large portion of CO
may have a stronger impact on the frequency of Mayer waves than other
vascular beds, such as the skin in a thermoneutral environment.
However, these considerations would also imply that the frequency of
Mayer waves may change if the distribution of CO to the individual
organs is altered. As an example, during heat stress a larger share of
CO is directed to the skin that responds relatively slowly to
sympathetic stimuli (21, 25). Thus one would expect that
Mayer waves are shifted toward lower frequencies during heat exposure.
In accordance with this hypothesis, it has been demonstrated that heat
stress in rats is associated with a pronounced increase in
low-frequency BP power in a frequency band below 0.2 Hz
(23). On the basis of these considerations, we propose
that investigation of the frequency of Mayer waves in addition to
low-frequency BP power may provide a more complete picture of
sympathetic control of the circulation than looking at low-frequency BP
power alone. This approach has been considered by Takalo et al.
(26, 27) who found that the median frequency of the Mayer
waves is shifted toward lower frequencies in borderline hypertensive
patients compared with normotensive subjects. More such studies are
needed to critically appraise the clinical importance of the frequency
of spontaneously occurring Mayer waves.
| |
ACKNOWLEDGEMENTS |
The authors thank Dipl. Ing. B. D. Röhl for technical assistance.
| |
FOOTNOTES |
Address for reprint requests and other correspondence:
H. M. Stauss, Dept. of Physiology, Humboldt-Univ. Berlin
(Charité), Tucholskystrasse 2, 10117 Berlin, Germany (E-mail:
harald.stauss{at}rz.hu-berlin.de).
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
10.1152/ajpregu.00307.2001
| |
REFERENCES |
1.
Anderson, EA,
Wallin BG,
and
Mark AL.
Dissociation of sympathetic nerve activity in arm and leg muscle during mental stress.
Hypertension
9:
III114-III119,
1987.
2.
Bertram, D,
Barres C,
Cheng Y,
and
Julien C.
Norepinephrine reuptake, baroreflex dynamics, and arterial pressure variability in rats.
Am J Physiol Regulatory Integrative Comp Physiol
279:
R1257-R1267,
2000[Abstract/Free Full Text].
3.
Bertram, D,
Barres C,
Cuisinaud G,
and
Julien C.
The arterial baroreceptor reflex of the rat exhibits positive feedback properties at the frequency of Mayer waves.
J Physiol (Lond)
513:
251-261,
1998[Abstract/Free Full Text].
4.
Cooke, WH,
Cox JF,
Diedrich AM,
Taylor JA,
Beightol L,
Ames JE,
Hoag JB,
Seidel H,
and
Eckberg DL.
Controlled breathing protocols probe human autonomic cardiovascular rhythms.
Am J Physiol Heart Circ Physiol
274:
H709-H718,
1998[Abstract/Free Full Text].
5.
DiBona, GF.
Neural control of the kidney: functionally specific renal sympathetic nerve fibers.
Am J Physiol Regulatory Integrative Comp Physiol
279:
R1517-R1524,
2000[Abstract/Free Full Text].
6.
DiBona, GF,
and
Sawin LL.
Renal hemodynamic effects of activation of specific renal sympathetic nerve fiber groups.
Am J Physiol Regulatory Integrative Comp Physiol
276:
R539-R549,
1999[Abstract/Free Full Text].
7.
Grisk, O,
and
DiBona GF.
Influence of arterial baroreceptors and intracerebroventricular guanabenz on synchronized renal nerve activity.
Acta Physiol Scand
163:
209-218,
1998[Web of Science][Medline].
8.
Grisk, O,
Frey BA,
Uber A,
and
Rettig R.
Sympathetic activity in early renal posttransplantation hypertension in rats.
Am J Physiol Regulatory Integrative Comp Physiol
279:
R1737-R1744,
2000[Abstract/Free Full Text].
9.
Guild, SJ,
Austin PC,
Navakatikyan M,
Ringwood JV,
and
Malpas SC.
Dynamic relationship between sympathetic nerve activity and renal blood flow: a frequency domain approach.
Am J Physiol Regulatory Integrative Comp Physiol
281:
R206-R212,
2001[Abstract/Free Full Text].
10.
Janssen, BJA,
Oosting J,
Slaaf DW,
Persson PB,
and
Struyker-Boudier HAJ
Hemodynamic basis of oscillations in systemic arterial pressure in conscious rats.
Am J Physiol Heart Circ Physiol
269:
H62-H71,
1995[Abstract/Free Full Text].
11.
Japundzic, N,
Grichois ML,
Zitoun P,
Laude D,
and
Elghozi JL.
Spectral analysis of blood pressure and heart rate in conscious rats: Effect of autonomic blockers.
J Auton Nerv Syst
30:
91-100,
1990[Web of Science][Medline].
12.
Julien, C,
Zhang ZQ,
Cerutti C,
and
Barres C.
Hemodynamic analysis of arterial pressure oscillations in conscious rats.
J Auton Nerv Syst
50:
239-252,
1995[Web of Science][Medline].
13.
Kikuya, M,
Hozawa A,
Ohokubo T,
Tsuji I,
Michimata M,
Matsubara M,
Ota M,
Nagai K,
Araki T,
Satoh H,
Ito S,
Hisamichi S,
and
Imai Y.
Prognostic significance of blood pressure and heart rate variabilities: The Ohasama study.
Hypertension
36:
901-906,
2000[Abstract/Free Full Text].
14.
Leonard, BL,
Evans RG,
Navakatikyan MA,
and
Malpas SC.
Differential neural control of intrarenal blood flow.
Am J Physiol Regulatory Integrative Comp Physiol
279:
R907-R916,
2000[Abstract/Free Full Text].
15.
Leonard, BL,
Malpas SC,
Denton KM,
Madden AC,
and
Evans RG.
Differential control of intrarenal blood flow during reflex increases in sympathetic nerve activity.
Am J Physiol Regulatory Integrative Comp Physiol
280:
R62-R68,
2001[Abstract/Free Full Text].
16.
Malpas, SC,
Hore TA,
Navakatikyan M,
Lukoshkova EV,
Nguang SK,
and
Austin PC.
Resonance in the renal vasculature evoked by activation of the sympathetic nerves.
Am J Physiol Regulatory Integrative Comp Physiol
276:
R1311-R1319,
1999[Abstract/Free Full Text].
17.
Mancia, G,
Frattola A,
Parati G,
Santucciu C,
and
Ulian L.
Blood pressure variability and organ damage.
J Cardiovasc Pharmacol
24, SupplA:
S6-S11,
1994.
18.
Mayer, S.
Studien zur Physiologie des Herzens und der Blutgefässe. V über spontane Blutdruckschwankungen
Sitzungsb d k Akad d W math nat Cl
74:
281-307,
1876.
19.
Okada, Y,
and
Ninomiya I.
Different cardiac and renal inhibitory and excitatory areas in rabbit hypothalamus.
Am J Physiol Heart Circ Physiol
244:
H832-H838,
1983.
20.
Persson, PB,
Stauss H,
Chung O,
Wittmann U,
and
Unger T.
Spectrum analysis of sympathetic nerve activity and blood pressure in conscious rats.
Am J Physiol Heart Circ Physiol
263:
H1348-H1355,
1992[Abstract/Free Full Text].
21.
Stauss, HM,
Anderson EA,
Haynes WG,
and
Kregel KC.
Frequency response characteristics of sympathetically-mediated vasomotor waves in humans.
Am J Physiol Heart Circ Physiol
274:
H1277-H1283,
1998[Abstract/Free Full Text].
22.
Stauss, HM,
and
Kregel KC.
Frequency response characteristic of sympathetic mediated vasomotor waves in conscious rats.
Am J Physiol Heart Circ Physiol
271:
H1416-H1422,
1996[Abstract/Free Full Text].
23.
Stauss, HM,
Morgan DA,
Anderson KE,
Massett MP,
and
Kregel KC.
Modulation of baroreflex sensitivity and spectral power of blood pressure by heat stress and aging.
Am J Physiol Heart Circ Physiol
272:
H776-H784,
1997[Abstract/Free Full Text].
24.
Stauss, HM,
Persson PB,
Johnson AK,
and
Kregel KC.
Frequency response characteristic of autonomic nervous system function in conscious rats.
Am J Physiol Heart Circ Physiol
273:
H786-H795,
1997[Abstract/Free Full Text].
25.
Stauss, HM,
Stegmann JU,
Persson PB,
and
Häbler HJ.
Frequency response characteristics of sympathetic transmission to skin vascular smooth muscles in rats.
Am J Physiol Regulatory Integrative Comp Physiol
277:
R591-R600,
1999[Abstract/Free Full Text].
26.
Takalo, R,
Korhonen I,
Majahalme S,
Tuomisto M,
and
Turjanmaa V.
Circadian profile of low-frequency oscillations in blood pressure and heart rate in hypertension.
Am J Hypertens
12:
874-881,
1999[Web of Science][Medline].
27.
Takalo, R,
Korhonen I,
Turjanmaa V,
Majahalme S,
Tuomisto M,
and
Uusitalo A.
Frequency shift in baroregulatory oscillation in borderline hypertensive subjects.
Am J Hypertens
10:
500-504,
1997[Web of Science][Medline].
28.
Ursino, M,
Cavalcanti S,
Bertuglia S,
and
Colantuoni A.
Theoretical analysis of complex oscillations in multibranched microvascular networks.
Microvasc Res
51:
229-249,
1996[Web of Science][Medline].
Am J Physiol Regul Integr Comp Physiol 282(5):R1468-R1476
0363-6119/02 $5.00
Copyright © 2002 the American Physiological Society
TOP
ABSTRACT
INTRODUCTION
