Reflex Effects on Renal Nerve Activity Characteristics in Spontaneously Hypertensive Rats
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.
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 SHR×WKY 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.
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.
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 20 000× 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.
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/min×45 to 60 seconds IV) and increased from that level to approximately 200 mm Hg with an infusion of phenylephrine (2 to 5 mg/min×45 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.
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 5×4 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 : where y is percentage of control RSNA and x is MAP. The parameters represent P1, range of change in y; P2, coefficient for calculation of gain; P3, MAP at midrange of the curve; P4, minimum value of y (lower plateau), and P1+P4, maximum value of y (upper plateau). The maximal gain (Gmax, where MAP=P3) is −(P1) · (P2)/4. MAP at saturation (MAPsat) is P3+1.317/P2 and MAP at threshold (MAPthr) is P3−1.317/P2. The mean P1 through P4 values were derived for each relationship in each rat; these values were then averaged to give mean values of P1 through P4 for each group. The mean P1 through P4 values were used to construct a mean curve for each group. We have demonstrated previously that this mean curve is a close fit to the mean±SE of the raw data.10
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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 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 WKY×SHR 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.
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.
Selected Abbreviations and Acronyms
|MAP||=||mean arterial pressure|
|MRAP||=||mean right atrial pressure|
|PAP||=||pulsatile arterial pressure|
|RSNA||=||renal sympathetic nerve activity|
|SHR||=||spontaneously hypertensive rat(s)|
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.
- Revision received March 26, 1997.
- Accepted May 9, 1997.
Malpas SC, Ninomiya I. A new approach to analysis of synchronized sympathetic nerve activity. Am J Physiol.. 1992;263:H1311-H1317.
Coote JH, Sato Y. Reflex regulation of sympathetic activity in the spontaneously hypertensive rat. Circ Res.. 1977;40:571-577.
Ricksten S-E, Thorén P. Reflex control of sympathetic nerve activity and heart rate from arterial baroreceptors in conscious spontaneously hypertensive rats. Clin Sci.. 1981;61:169s-172s.
DiBona GF, Jones SY. Analysis of renal sympathetic nerve responses to stress. Hypertension.. 1995;25:531-538.
Folkow BF. Physiological aspects of primary hypertension. Physiol Rev.. 1982;62:347-504.
Grisk O, DiBona GF. Cardiopulmonary baroreflex in NaCl-induced hypertension in borderline hypertensive rats. Hypertension.. 1997;29:464-470.
DiBona GF, Jones SY, Brooks VL. ANG II receptor blockade and arterial baroreflex regulation of renal nerve activity in cardiac failure. Am J Physiol.. 1996;269:R1189-R1196.
DiBona GF, Jones SY, Sawin LL. Reflex influences on renal nerve activity characteristics in nephrosis and heart failure. J Am Soc Nephrol. In press.
Veldhuis JD, Johnson ML. Cluster analysis: a simple, versatile, and robust algorithm for endocrine pulse detection. Am J Physiol.. 1986;250:E486-E493.
Malpas SC, Bendle RD, Head GA, Ricketts JH. Frequency and amplitude of sympathetic discharges by baroreflexes during hypoxia in conscious rabbits. Am J Physiol.. 1996;271:H2563-H2574.
DiBona GF, Sawin LL, Jones SY. Differentiated sympathetic neural control of the kidney. Am J Physiol.. 1996;271:R84-R90.