(Hypertension. 1997;30:1089-1096.)
© 1997 American Heart Association, Inc.
Articles |
Reflex Effects on Renal Nerve Activity Characteristics in Spontaneously Hypertensive Rats
From the Department of Internal Medicine, University of Iowa College of Medicine, and Department of Veterans Affairs Medical Center, Iowa City, Iowa.
Correspondence to Gerald F. DiBona, MD, Dept of Internal Medicine, University of Iowa College of Medicine, 200 Hawkins Dr, Iowa City, IA 52242. E-mail gerald-dibona{at}uiowa.edu
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Abstract |
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Abstract The effects of arterial and cardiac baroreflex activation on the discharge characteristics of renal sympathetic nerve activity were evaluated in conscious spontaneously hypertensive and Wistar-Kyoto rats. In spontaneously hypertensive rats compared with Wistar-Kyoto rats, (1) arterial baroreflex regulation of renal sympathetic nerve activity was reset to a higher arterial pressure and the gain was decreased and (2) cardiac baroreflex regulation of renal sympathetic nerve activity exhibited a lower gain. With the use of sympathetic peak detection analysis, the inhibition of integrated renal sympathetic nerve activity, which occurred during both increased arterial pressure (arterial baroreflex) and right atrial pressure (cardiac baroreflex), was due to parallel decreases in peak height with little change in peak frequency in both spontaneously hypertensive and Wistar-Kyoto rats. Arterial and cardiac baroreflex inhibition of renal sympathetic nerve activity in Wistar-Kyoto and spontaneously hypertensive rats is due to a parallel reduction in the number of active renal sympathetic nerve fibers.
Key Words: sympathetic nervous system • rats, inbred strains • baroreceptor
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Introduction |
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Arterial baroreflex regulation of RSNA has been well characterized. When carotid sinus pressure is forced from below to above resting values, the response of RSNA is a decreasing sigmoidal relationship. When recorded from multifiber preparations, RSNA occurs as rhythmic bursts or peaks that exhibit cardiac cycle synchrony. The individual peaks are characterized1 by variable peak height, a relatively constant peak duration, and a peak frequency that is not always the same as the cardiac cycle frequency or heart rate. When RSNA is measured as integrated voltage over time, changes in total RSNA can be due to some combination of changes in peak height, peak duration, and/or peak frequency.
Studies in anesthetized normal cats2 demonstrated that peak frequency was decreased by arterial baroreflex activation (increased baroreceptor afferent activity) and increased by arterial baroreflex deactivation (decreased baroreceptor afferent activity), whereas peak height and peak duration were unaffected. Thus, peak frequency was closely and inversely related to baroreceptor afferent activity. When postganglionic cardiac sympathetic nerve activity was analyzed before and after successive denervation of T1-5 preganglionic nerves to the stellate ganglion, peak height was progressively decreased while peak duration and peak frequency were unchanged.3 Thus, peak height reflects the number of active nerve fibers.
Both arterial and cardiac baroreflex regulation of RSNA in SHR is altered from that in WKY. In the arterial baroreflex, there is resetting of the relationship between arterial pressure and RSNA toward the higher level of arterial pressure seen in SHR, and the gain may be decreased compared with WKY.4 5 In the cardiac baroreflex, the gain is less in SHR compared with WKY.6 In previous studies of the effect of an acute environmental stress, air jet stress, on responses of RSNA in conscious SHR and WKY, the increase in RSNA was associated with an increase in both peak frequency and peak height.7 Because air jet stress represents a defense reaction that is known to override or deactivate the arterial baroreflex,8 the increase in peak frequency was expected from the previous findings (see above). However, the increase in peak height, reflecting an increased number of active fibers, was not. In the assessment of cardiac baroreflex regulation of RSNA in an SHRxWKY backcross population, the decrease in RSNA was associated with a decrease in peak height, whereas peak frequency showed a slight increase.9 These responses in this backcross population derived from SHR and WKY were different from predicted and suggested that arterial and cardiac baroreflex regulation of the synchronized sympathetic discharge that constitutes RSNA may differ between the parental WKY and SHR strains.
The purpose of this investigation was to test the hypothesis that the regulation of peak height and peak frequency of synchronized renal sympathetic discharge during arterial and cardiac baroreceptor activation is different in WKY and SHR.
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Methods |
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Rats
Male SHR and WKY (12 weeks of age) were purchased from Taconic Farms (Germantown, NY), housed in individual cages, and fed normal rat pellet diet with tap water drinking fluid until the time of study at age 16 weeks. All animal procedures were in accordance with the guidelines of the University of Iowa Animal Care and Use Committee.
Instrumentation
Under methohexital anesthesia, 50 mg/kg IP
(Brevital, Eli Lilly & Co), catheters were inserted into the right
carotid artery, the right atrium through the right jugular vein, and
the right femoral vein. Isotonic saline was infused at 0.05 mL/min for
the duration of the surgery. At the conclusion of surgery, the isotonic
saline infusion was stopped, and the catheters were exteriorized at the
back of the neck, filled with isotonic saline containing 500 IU/mL
heparin, and plugged.
The left kidney was exposed via a left flank incision, and a renal nerve bundle was dissected in the angle between the abdominal aorta and the renal artery. The renal nerve bundle was placed on a bipolar platinum electrode (Cooner Wire) for recording of RSNA. The renal nerve signal was amplified 20 000x and filtered (30 Hz low and 3000 Hz high) with a Grass model P511 bandpass amplifier via a Grass model HIP511 high-impedance probe. The amplified and filtered signals were displayed on an oscilloscope (Tektronix 5113), an audio monitor (Grass model AM 8), and a polygraph (Grass model 7). The RSNA signal was full-wave rectified and integrated with a rectifying voltage integrator (Grass model 7P3) at a time constant of 20 milliseconds. This was further filtered at 35 Hz to yield a pulsatile voltage signal where individual bursts in the neurogram are smoothed. The quality of the RSNA signal was assessed by its pulse synchronous rhythmicity; signal-to-noise ratio ranged between 3:1 and 5:1. A further assessment was made during an intravenous injection of phenylephrine; as MAP increased, RSNA decreased. When an optimal signal was observed, the electrode was fixed to the renal nerve bundle with silicone cement (Wacker Sil-Gel 601, Wacker Chemie). The electrode cable was secured in position by suturing to the abdominal trunk muscles and tunneled to the back of the neck, where it was exteriorized. The flank incision was closed in layers.
Rats were returned to individual home cages and given free access to normal rat pellet diet with tap water drinking fluid.
Experimental Protocol
The day after instrumentation, the rats were studied conscious
and unrestrained in their individual home cages. The
arterial catheter was connected to a pressure transducer
(Statham P23Db, Gould Instruments) coupled to a polygraph (model 7,
Grass Instruments) for measurement of PAP and MAP. HR was measured with
a Grass 7P4 tachograph driven by the PAP wave form. The right atrial
catheter was connected to a pressure transducer (Statham P23Db, Gould
Instruments) coupled to a polygraph (model 7, Grass Instruments) for
measurement of pulsatile pressure and MRAP. The RSNA electrode cable
was connected to the Grass model HIP511 high-impedance probe. The
femoral vein catheter was connected to an infusion pump set to deliver
isotonic saline at 0.05 mL/min.
After 60 minutes of equilibration, continuous measurements of PAP, MAP, MRAP, HR, and integrated RSNA were initiated. After a 10-minute control period, arterial baroreflex control of RSNA was tested. MAP was lowered from its control level to approximately 40 mm Hg with an infusion of nitroprusside (0.4 µg/minx45 to 60 seconds IV) and increased from that level to approximately 200 mm Hg with an infusion of phenylephrine (2 to 5 mg/minx45 to 60 seconds IV). The time between termination of the nitroprusside infusion and initiation of the phenylephrine infusion was 10 to 20 seconds. The changes in MAP were purposely kept to short duration (necessitating single infusion rates) to minimize the duration and magnitude of any changes in intracardiac pressures that may have influenced other receptors involved in the regulation of RSNA. Because these studies were done in conscious rats, assessment of this possibility by repeating these studies after vagotomy was not possible. The phenylephrine infusion was stopped, and 30 minutes was allowed for all measurements to return to their respective control levels. The evaluation of arterial baroreflex regulation of RSNA is not affected by the choice of carotid10 versus femoral11 arterial catheterization for the measurement of arterial pressure.
After another 10-minute control period, cardiac baroreflex control of RSNA was tested. Isotonic saline was infused rapidly (12.5 mL/kg per minute IV) to produce an increase in MRAP of 3 mm Hg within 100 to 120 seconds. Measurements were continued for another 5 minutes beyond the end of acute volume loading. The rats were then killed with an overdose of methohexital. RSNA was recorded 30 minutes after death as a measurement of background noise.
Data Analysis
Sympathetic Peak Detection Algorithm
Analog data (PAP, MAP, HR, MRAP, and RSNA) were recorded on
videotape with a recording adapter (4000 PCM, Vetter Co). PAP,
RSNA, and MRAP were acquired off-line from the videotape at 200 Hz
using a Lab-PC+ data acquisition card and Lab View 4.1 software
(National Instruments). The sympathetic peak detection algorithm for
analysis of characteristics of synchronized renal sympathetic
nerve discharges, Sympathetic Peak Detection Program version 3.0, was
kindly provided by S.C. Malpas, Department of Physiology, University of
Auckland Medical School (New Zealand).1 This program is
based on the cluster analysis algorithm developed for
investigation of pulsatile hormone release.1 12 Based on a
5x4 cluster configuration and a 4.1 t statistic, the
pulsatile voltage signal is scanned for significant increases and
decreases in a small cluster of values (cluster width, 20
milliseconds).1 7 12 After all significant increases
(peaks) and decreases (nadirs) of synchronized renal sympathetic nerve
discharge are marked, the height of each peak (in µV) and the peak
frequency (in Hz) are calculated.
In a preliminary study, the impact of the chosen threshold voltage value on the detection of peaks was assessed. Three values of threshold voltage were applied to recordings from an SHR during resting conditions (control MAP) and phenylephrine infusion (increased MAP), and the detection of peaks and the distribution of peak heights and peak-to-peak intervals (inverse of peak frequency) were compared. The three values of threshold voltage were 0 µV, 10 µV (10% to 15% of the average maximum peak height from the preliminary RSNA recording), and 10.62 µV (postmortem death signal in this rat). As presented in "Results," the distribution of peak heights and peak-to-peak intervals was not significantly affected by the choice of threshold voltage. Therefore, the postmortem signal for each rat was used as the threshold voltage for that rat.
The peak height is a measure of the number of active nerve fibers,3 and the peak frequency is a measure of the periodicity (reciprocal of the peak-to-peak interval) of the synchronized discharges.2 Additional outputs are MAP, HR, MRAP, and mean integrated RSNA either for a specified time bin (1 second) or per cardiac cycle. To allow for comparisons of peak height between rats, the mean peak height during each control period was set equal to 100%, and changes after interventions were expressed as a percentage of this value and are presented as relative peak heights.
During arterial baroreflex testing, it was found that the plots of changes in RSNA and peak height versus MAP were sigmoidal, whereas the plot of changes in peak frequency versus MAP was linear. During cardiac baroreflex testing, it was found that the plots of changes in RSNA, peak height, and peak frequency versus MRAP were linear. The four-parameter logistic regression equation (see below) was used for analysis of the sigmoidal relationships and linear regression for the analysis of the linear relationships.
Arterial Baroreflex Sensitivity
For evaluation of arterial baroreflex control of
RSNA, MAP was plotted against RSNA, expressed as a percentage of
control period RSNA, over the MAP range from 40 to 200 mm Hg. The
resultant sigmoidal relationship, representing the overall
arterial baroreflex, was analyzed with a four
parameter logistic regression equation13 :
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Cardiac Baroreflex Sensitivity
For evaluation of cardiac baroreflex control of RSNA, MRAP was
plotted against RSNA, expressed as a percentage of control period RSNA,
over the MRAP range from control value to control value plus 3
mm Hg. The resultant linear relationship, representing the
overall cardiac baroreflex, was analyzed with linear regression
analysis.
Statistical Analysis
Single comparisons between WKY and SHR were performed with the
unpaired t test. The significance level was set at
P<.05. All data in text, tables, and figures are
presented as mean±SE.
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Results |
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Influence of Threshold on Detection and Characterization of Peaks
During resting conditions (control MAP), a steady-state time period of 1.9 minutes containing 730 sympathetic peaks was examined. The frequency histogram of intervals between sympathetic peaks exhibited one main cardiac-related rhythm and several lower occurrence rhythms with modes two or three times that of the main rhythm (harmonics) (Fig 1A
). The peak height of
individual sympathetic peaks exhibited large variation, ranging from
approximately 30% to 200% of the average peak height without a clear
mode (Fig 1B). The distribution of peak-to-peak intervals and peak
heights was not affected by the choice of threshold voltage level for
detection of sympathetic peaks.
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), 10 µV (10% to
15% of the average maximum peak height from the preliminary RSNA
recording, 
), and 10.62 µV (postmortem death signal in
this rat, 
).
During phenylephrine infusion (increased MAP), a short time
period when MAP had reached a near-maximum plateau of 0.25 minute
containing 98 peaks was examined. The frequency histogram of intervals
between sympathetic peaks exhibited no predominant rhythm; there were
several low-occurrence rhythms distributed both slightly above and
slightly below that of the cardiac rhythm (heart period) (Fig 1C
). The
peak height of individual sympathetic peaks exhibited a single
predominant modal peak encompassing the range of 14 to 20 µV (33% to
47% of the average peak height during control MAP), with very few
peaks with peak heights greater than 20 µV (Fig 1D). The distribution
of peak-to-peak intervals and peak heights was not affected by the
choice of threshold voltage level for detection of sympathetic
peaks.
The use of a threshold voltage of 0 µV (RSNA uncorrected for the
postmortem signal) or 10.62 µV (RSNA corrected for the postmortem
death signal) yielded similar patterns of detection and
characterization of peaks. This suggests that although there is low
voltage activity (<10 µV) in the RSNA signal, even when it is
analyzed with a threshold voltage of 0 µV, it does not meet
the criteria for being identified as a synchronized renal sympathetic
nerve discharge (Fig 1B). This is possibly related to alterations in
shape. In addition, during increased MAP, when peak height is
decreasing, the possibility exists that the use of too high a threshold
voltage would bias against the detection of small peaks that truly
represent synchronized renal sympathetic nerve discharge.
Because such small peaks would not be detected, peak frequency would
also decrease (increased peak-to-peak interval). However, during
increased MAP, whereas peak height decreased markedly, there were no
peaks with peak heights less than 14 µV, ie, that would have been
eliminated using a threshold voltage of 10.62 µV, the postmortem
signal (Fig 1D). Also, the distribution of peak-to-peak interval was
not shifted to higher values (Fig 1C).
Arterial Baroreflex Regulation of RSNA
In the control period prior to arterial baroreflex
testing (Table 1), SHR had significantly
higher MAP, HR, and RSNA than WKY. In SHR, the higher RSNA was due to a
larger peak height, whereas peak frequency was similar. Because it is
not strictly possible to reliably compare multifiber sympathetic nerve
activity recordings between rats or groups of rats due to
differences in numbers of active fibers on the electrode or differences
in nerve electrode contact, these results should be interpreted with
caution.
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Fig 2 shows mean logistic regression
equation curves for the relationship between RSNA and MAP derived from
the mean parameters P1 through P4 for
WKY and SHR seen in Table 2. Whereas the
maximum RSNA (P1+P4) achieved during decreased
MAP was similar in WKY and SHR, the minimum RSNA (P4)
achieved during increased MAP was lower in WKY than SHR; thus, the
range (P1) was less in SHR than WKY.
Gmax was less and the midpoint (P3)
was greater in SHR than WKY. The SHR curve is reset to a higher level
of MAP and the magnitude of resetting (difference in P3
values, 32 mm Hg) is similar to the magnitude of the difference
in resting MAP (29 mm Hg). The MAPs for both threshold and
saturation were greater in SHR than WKY.
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The net result is that during increases in MAP, RSNA is greater in SHR
than WKY at every level of MAP. RSNA may be considered the integrated
product of the peak height and the peak frequency of the peaks in
synchronized sympathetic discharge. To determine whether the
differences in arterial baroreflex regulation of RSNA in
WKY and SHR derived from differences in the responses of peak height
and peak frequency in WKY and SHR, these elements were analyzed
using the sympathetic peak detection algorithm. Fig 3 shows absolute values for MAP (mm Hg),
RSNA (µV), peak height (µV), and peak frequency (Hz) plotted
as 1-second averages (200 Hz sampling rate) against time in a single
SHR. The data set begins at the MAP minimum during nitroprusside
administration and ends at the MAP maximum during
phenylephrine administration. During the progressive
increase in MAP, both peak height and RSNA decrease in a similar
sigmoidal fashion to minimum plateaus, whereas peak frequency shows a
slight increase.
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Fig 4 shows mean logistic regression
equation curves for the relationship between peak height and MAP
derived from the mean parameters P1 through
P4 for WKY and SHR seen in Table 2. Although the maximum peak height
(P1+P4) achieved during decreased MAP was similar
in WKY and SHR, the minimum peak height (P4) achieved during
increased MAP was lower in WKY than SHR; thus, the range
(P1) was less in SHR than WKY. Gmax
was less and the midpoint (P3) was greater in SHR than WKY.
The SHR curve is reset to a higher level of MAP and the magnitude of
resetting (difference in P3 values, 32 mm Hg) is
similar to the magnitude of the difference in resting MAP (29
mm Hg). The MAPs for both threshold and saturation were greater in SHR
than WKY.
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In both WKY and SHR, the relationships of both RSNA and peak height to MAP were sigmoidal; however, the relationship of peak frequency to MAP was not sigmoidal. At best, the relationships could be described as linear with very low but positive values for both slope and correlation coefficients. The slope was 0.013±0.007 Hz/mm Hg in WKY and 0.013±0.004 Hz/mm Hg in SHR; these values are not significantly different. The correlation coefficients ranged from 0.08 to 0.58 in WKY (3/9 significant, 6/9 not significant) and 0.01 to 0.53 in SHR (4/9 significant, 5/9 not significant).
Thus, comparing WKY and SHR, the differences in the RSNA versus MAP
relationships were similar to the differences in the peak height versus
MAP relationships. Furthermore, in comparing the RSNA versus MAP and
peak height versus MAP relationships within WKY and SHR, it is apparent
that they were similar. Fig 5 shows RSNA
and peak height, as a percentage of control, plotted against MAP in a
single WKY. As MAP increases from a minimum during nitroprusside
administration to a maximum during phenylephrine
administration, RSNA and peak height respond in a parallel negative
sigmoidal fashion. Peak frequency was 6.97 Hz at minimum MAP and 7.12
at maximum MAP. This is further seen in Table 2, when the values for
P1 through P4 for RSNA versus MAP are compared
with the values for P1 through P4 for peak height
versus MAP in both WKY and SHR; there are no significant
differences.
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Cardiac Baroreflex Regulation of RSNA
In the control period prior to cardiac baroreflex testing (Table 3), SHR had significantly higher MAP, HR,
and RSNA than WKY. In SHR, the higher RSNA was due to larger peak
height, whereas peak frequency was similar.
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During the rapid increase in MRAP, MAP and HR decreased slightly in
both WKY and SHR. At the end of the volume loading, MAP was 118±4
mm Hg and HR was 331±8 bpm in WKY; the values were 153±7 mm Hg
and 400±10 bpm in SHR. During the rapid increase in MRAP, both RSNA
and peak height decreased in a linear fashion. The magnitude of the
reduction in both RSNA and peak height was greater in WKY than SHR.
Within strain, however, the magnitude of the reduction in RSNA and peak
height was similar. Linear regression was used to calculate the slopes
of the relationships between increases in MRAP and decreases in RSNA
and peak height (Table 4). The
correlation coefficients ranged between .75 and .90 for each
relationship for each rat (P<.01). The gain (slope) of the
overall cardiac baroreflex control of RSNA (%RSNA/mm Hg) was
significantly greater in WKY than SHR. Similar to RSNA, the slope of
the peak height versus MRAP relationship (% Peak Height/mm Hg) was
significantly greater in WKY than SHR. The relationship of peak
frequency to MRAP could be described at best as linear with very low
but positive values for slope (Peak Frequency/mm Hg) and correlation
coefficients that ranged from .01 to .77 in WKY (3/9 significant, 6/9
not significant) and .01 to .38 in SHR (5/9 significant, 4/9 not
significant).
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When comparing WKY and SHR, the differences in the RSNA versus MRAP
relationships were similar to the differences in the peak height versus
MRAP relationships, ie, greater slopes in WKY than in SHR. Furthermore,
in comparing the RSNA versus MRAP and peak height versus MRAP
relationships within WKY and SHR, it is apparent that they were
similar. This is seen in Fig 6, which
plots the change in RSNA versus the change in peak height, both as a
percentage of control (1-second averages, 200 Hz sampling rate), during
a volume load which increased MRAP by 3.1 mm Hg in a single WKY.
It is evident that the decreases in RSNA were well correlated with
decreases in peak height. During the same time, peak frequency
increased from 6.73 to 7.06. For the groups, when the slope values for
RSNA versus MRAP are compared with the slope values for peak height
versus MRAP within WKY and within SHR, there are no significant
differences.
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Discussion |
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Arterial Baroreflex
Arterial baroreflex regulation of RSNA was different in SHR than in WKY. The relationship between RSNA and MAP was reset toward the higher level of MAP seen in SHR, and the gain was decreased by 58% compared with WKY. The resetting was essentially complete, as estimated by comparing the difference between the P3 (midpoint) values for the curves of RSNA versus MAP in SHR and WKY of 32 mm Hg with the difference between the resting MAP values in SHR and WKY of 29 mm Hg. These findings concerning overall arterial baroreflex regulation of SHR and WKY are similar to those in the literature.4 5
As applied to RSNA, sympathetic peak detection analysis measures both the frequency (inverse of peak-to-peak interval) and the amplitude (peak height) of synchronized renal sympathetic nerve discharges (sympathetic peaks). The summation of frequency and amplitude closely approximates the 1-second average of the original integrated neurogram, ie, RSNA. Previous studies suggested that the frequency reflects the inherent generation of discharges by brain stem circuits, and the amplitude reflects the number of active fibers within each discharge.2 3 Based on the possibility that these two components, frequency and amplitude, might be differentially affected by distinct stimuli, the hypothesis was put forth that these two components are independently controlled and generated by the central nervous system.14 Initial studies of RSNA in anesthetized cats supported this view in that asphyxia increased amplitude but not frequency,15 whereas arterial baroreceptor stimulation decreased frequency but did not affect amplitude.2 However, when arterial baroreflex regulation of RSNA was more comprehensively assessed in conscious rabbits using large decreases and increases in arterial pressure, it was noted that the decreasing sigmoidal relationship of RSNA with arterial pressure was mirrored in the responses of both amplitude and frequency.16 That is, as arterial pressure was decreased, RSNA, amplitude, and frequency increased in parallel to a maximum plateau, and as arterial pressure was increased, RSNA, amplitude, and frequency decreased in parallel to a minimum plateau. The parameters (lower and upper plateaus, range, arterial pressure at midpoint, Gmax) of the logistic equations used to fit the responses of RSNA, amplitude, and frequency (when converted to normalized units) to the induced changes in arterial pressure were not different. Thus, in the conscious rabbit, arterial baroreceptor stimulation decreases RSNA via parallel and nearly identical decreases in both amplitude and frequency of sympathetic peaks. This implies a similar reduction in both the number of active fibers and the firing frequency of those active fibers.
However, this is not the case in both conscious WKY and SHR, where arterial baroreceptor stimulation decreases RSNA nearly exclusively via decreases in peak height with little reduction being observed in peak frequency. This pattern of response was qualitatively and quantitatively similar in WKY and SHR. This implies a predominant reduction in the number of active fibers with little change in the firing frequency of those active fibers. Thus, during arterial baroreflex activation, increased afferent baroreceptor nerve activity decreases the number of active fibers contributing to RSNA, whereas during arterial baroreflex deactivation, decreased afferent baroreceptor nerve activity increases the number of active fibers contributing to RSNA. These results are in accordance with the results of studies with electrical stimulation of the aortic depressor nerve (increased afferent baroreceptor nerve activity), which decreased peak height but did not affect peak frequency.11
Cardiac Baroreflex
Cardiac baroreflex regulation of RSNA was different in SHR than in
WKY. As observed previously, the gain was greater in WKY than in
SHR.6 During the short time period of rapid volume loading
and increase in MRAP, the decrease in RSNA was linearly related to the
increase in MRAP. The decrease in peak height was also linearly related
to the increase in MRAP, and the gain of the relationship was similar
to that for RSNA and MRAP. This pattern of response was qualitatively
and quantitatively similar in WKY and SHR. In examination of the
changes in the characteristics of synchronized renal sympathetic
discharge that contributed to the decrease in RSNA, it was found that
decreases in peak height were closely correlated with decreases in
RSNA. Conversely, as observed previously in the WKYxSHR backcross
population,9 peak frequency increased slightly. This
indicates that cardiac baroreflex alterations in RSNA are produced by
altering the number of active fibers with little change in the firing
frequency of those active fibers. Thus, during cardiac baroreflex
activation, increased afferent vagal nerve activity decreases the
number of active fibers contributing to RSNA. These results are in
accordance with the results of studies with electrical stimulation of
the vagus nerve (increased afferent vagal nerve activity), which
decreased peak height and did not affect peak
frequency.11
Implications for Renal Function
Neither the mechanisms responsible for regulating the number of
active fibers (peak height) nor their location are known. However, the
possibility exists that alterations in RSNA that consist of changes in
both peak height and peak frequency have functionally different
implications for the kidney than those that consist only of changes in
peak height with relatively constant peak frequency or vice versa. For
example, a certain set of characteristic alterations in peak height
and/or peak frequency might preferentially influence the renal
vasculature (renal blood flow), whereas another set might
preferentially influence renal tubular sodium and water reabsorption or
renin secretion. This introduces the concept of functionally specific
subgroups of renal sympathetic nerve fibers. This concept has gained
significance with the increasing recognition17 that the
renal sympathetic nerves are not, under all activating circumstances, a
homogeneous and uniformly responsive population of fibers
as was initially thought.18 Efferent renal sympathetic
nerve fiber diameter measurements display a bimodal
distribution.17 Analysis of strength-duration
relationships during renal sympathetic nerve stimulation shows
different rheobase and chronaxie values for renal blood flow responses
compared with urinary flow rate responses.17 Whereas the
RSNA responses to arterial baroreflex and central and
peripheral chemoreflex stimulation are
homogeneous, when additional input stimuli are used, eg,
thermal cutaneous stimulation, a population of fibers exhibiting
heterogeneous responses can be identified.17
These observations suggest the existence of functionally specific
subgroups of renal sympathetic nerve fibers.
Conclusion
In summary, the inhibitory effects of
arterial and cardiac baroreceptor stimulation on RSNA in
WKY and SHR were associated with parallel reductions in the peak height
(amplitude), whereas the peak frequency of synchronized renal
sympathetic nerve discharge was unchanged. Therefore, the reductions in
RSNA are due to decreases in the number of active fibers with no change
in the firing frequency of the active fibers. This was qualitatively
and quantitatively similar in WKY and SHR.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This study was supported by grants DK-15843 and HL-55006 from the National Institutes of Health and grants from the Department of Veterans Affairs.
Received February 25, 1997; first decision March 26, 1997; accepted May 9, 1997.
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Malpas SC, Bendle RD, Head GA, Ricketts JH.
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