| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The Cardiovascular Center and the Departments of Internal Medicine and Physiology & Biophysics, The University of Iowa, Iowa City 52242; and the Department of Veterans Affairs Medical Center, Iowa City, Iowa, 52246
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Studies of genetically modified mice provide a powerful approach to investigate consequences of altered gene expression in physiological and pathological states. The goal of the present study was to characterize afferent, central, and efferent components of the baroreceptor reflex in anesthetized Webster 4 mice. Baroreflex and baroreceptor afferent functions were characterized by measuring changes in renal sympathetic nerve activity (RSNA) and aortic depressor nerve activity (ADNA) in response to nitroprusside- and phenylephrine-induced changes in arterial pressure. The data were fit to a sigmoidal logistic function curve. Baroreflex diastolic pressure threshold (Pth), the pressure at 50% inhibition of RSNA (Pmid), and baroreflex gain (maximum slope) averaged 74 ± 5 mmHg, 101 ± 3 mmHg, and 2.30 ± 0.54%/mmHg, respectively (n = 6). The Pth, Pmid, and gain for the diastolic pressure-ADNA relation (baroreceptor afferents) were similar to that observed for the overall reflex averaging 79 ± 9 mmHg, 101 ± 4 mmHg, and 2.92 ± 0.53%/mmHg, respectively (n = 5). The central nervous system mediation of the baroreflex and the chronotropic responsiveness of the heart to vagal efferent activity were independently assessed by recording responses to electrical stimulation of the left ADN and the peripheral end of the right vagus nerve, respectively. Both ADN and vagal efferent stimulation induced frequency-dependent decreases in heart rate and arterial pressure. The heart rate response to ADN stimulation was nearly abolished in mice anesthetized with pentobarbital sodium (n = 4) compared with mice anesthetized with ketamine-acepromazine (n = 4), whereas the response to vagal efferent stimulation was equivalent under both types of anesthesia. Application of these techniques to studies of genetically manipulated mice can be used to identify molecular mechanisms of baroreflex function and to localize altered function to afferent, central, or efferent sites.
pressoreceptors; blood pressure; aortic depressor nerve; sympathetic nerve activity; functional genomics
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
THE ARTERIAL BARORECEPTOR reflex is a major regulator of arterial pressure and cardiovascular function and has been studied extensively in numerous animal species and humans (3, 39). Despite the many advances made toward understanding the baroreceptor reflex, very little is known concerning the identity and function of molecules essential for sensory afferent, central, and efferent components of the reflex. For example, only recently have studies begun to elucidate the nature of the mechanoelectrical transducing ion channel on baroreceptor nerve terminals (9).
The recent explosion of gene discovery and the development of techniques to genetically modify intact animals provide new opportunities for discovery of novel mechanisms. Mice are particularly amenable to genetic manipulation, and their use in physiological studies is rapidly increasing (14, 26, 27). Recently, investigators have begun to study baroreflex function in mice; the majority of studies have examined reflex control of heart rate, and a few of these studies have provided quantitative measurements of baroreflex sensitivity (gain) in conscious and anesthetized mice (25, 30, 32, 34, 38). Studies of baroreflex control of heart rate are limited in that they do not provide information on the sensitivity for control of sympathetic nerve activity and vascular resistance (18, 19, 33). Furthermore, measurements of overall reflex function cannot discriminate effects on afferent, central nervous system (CNS), and efferent components of the reflex. Changes in one component of the reflex, e.g., effector organ responsiveness, may compensate for and obscure changes in another component of the reflex (6, 11, 12).
The major goals of the present study were 1) to characterize baroreceptor afferent sensitivity and reflex function in mice through direct electrophysiological recording of aortic depressor nerve activity (ADNA) and renal sympathetic nerve activity (RSNA) and 2) to independently assess the CNS mediation of the reflex and the chronotropic responsiveness of the heart to efferent vagal activity by recording responses to electrical stimulation of ADN afferents and vagus nerve efferents, respectively.
| |
MATERIALS AND METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Studies were performed on 36 male mice (Webster 4 strain, 25-35 g). The mice were anesthetized with either pentobarbital sodium (60 µg/g ip) or ketamine (91 µg/g ip) and acepromazine (1.8 µg/g ip). Supplemental doses of anesthetics were administered as needed to prevent eye blink and withdrawal reflexes and fluctuations in arterial blood pressure. Body temperature was maintained using a heating pad. The left femoral artery was cannulated with polyethylene tubing (PE-10 connected with PE-50). Arterial pressure was measured with a pressure transducer (COBE, CDX-III), and heart rate was derived from the arterial pressure pulse using a cardiotachometer (Beckman, 9857B). Both femoral veins were cannulated with polyethylene catheters (PE-10) for administration of drugs. A cervical midline incision was performed and the trachea was cannulated with polyethylene tubing (PE-90) to facilitate ventilation in the spontaneously breathing mice. All of the procedures carried out on the mice were approved by the University of Iowa Animal Care and Use Committee and followed the guidelines of the American Physiological Society.
Recording of RSNA. The left kidney was exposed retroperitoneally via a flank incision in mice anesthetized with pentobarbital sodium. A sympathetic nerve leading to the left kidney was identified between the renal artery and vein using a dissecting microscope. The nerve was isolated from surrounding connective tissue and placed on miniaturized bipolar platinum electrodes (0.12-mm outer diameter). The nerve and electrode were encased in Wacker silicone gel. Nerve activity was amplified using a high-impedance probe and a Grass band-pass amplifier (HIP 511J, 300 Hz-3 kHz). The neurogram was displayed on a dual-beam storage oscilloscope (Tektronix 5113) and listened to through an audio speaker. The frequency of spikes that exceeded a selected threshold voltage just above noise level was counted consecutively in 0.5-s bins using a nerve traffic analyzer (University of Iowa Bioengineering, 706C) (20, 21, 31, 33). Correct placement of the threshold level was confirmed by the elimination of counted RSNA during phenylephrine (PE)-induced increases in arterial pressure and after the death of the mice following the experiment. The phasic arterial pressure, mean arterial pressure, heart rate, and the ratemeter output of RSNA (spikes/s) were recorded on a chart recorder (Gould). In some experiments, the neurogram was recorded using a MacLab computerized data-acquisition system.
Recording of baroreceptor activity from the ADN.
The left ADN was identified in the cervical region using a dissecting
microscope in mice anesthetized with pentobarbital sodium. The nerve
was isolated from surrounding connective tissue and placed on
miniaturized bipolar platinum electrodes (0.12-mm outer diameter). The
ADNA was recorded using the same procedures as for recording RSNA. The
ADN was successfully identified in 18 of 28 mice by the characteristic
discharge of activity in phase with the arterial pressure pulse (Fig.
1A). In the majority of mice
(16 of 18), the left ADN existed as a separate nerve traversing the
cervical region between the left common carotid artery and trachea
before joining the superior laryngeal nerve. In two mice, the ADN
traveled with the cervical vagus nerve or sympathetic trunk before
projecting to the superior laryngeal nerve. Thirteen of the 18 preparations enabled functional studies to be performed (ADN recording,
n = 5; ADN stimulation, n = 8). Five of
the experiments failed because of either anesthesia-induced hypotension
or a poor signal-to-noise ratio in the nerve recording.
|
Measurement of responses to electrical stimulation of ADN. The left ADN was isolated and placed on a bipolar platinum electrode using the same procedures as described in the preceding section. The nerve was then crushed at a point caudal to the electrode. The nerve was stimulated with rectangular 10-V, 2-ms duration pulses that were delivered to the electrode at varying frequencies from a stimulator (Grass, model S44) through an isolation unit (Grass, SIU 5).
Measurement of responses to electrical stimulation of vagal efferent nerves. The right vagus nerve was isolated from surrounding connective tissue and sectioned. The cut peripheral end of the vagus nerve was placed on a bipolar platinum electrode and stimulated electrically as described for the ADN in the preceding section.
Experimental protocols. After completion of the surgical procedures, the mice were allowed to stabilize for a period of 20-30 min before beginning the protocols. Four groups of experiments were performed.
Baroreflex control of RSNA (n = 6). Baroreflex control of RSNA was evaluated by recording reflex changes in RSNA in response to changes in arterial pressure induced by a single intravenous injection of sodium nitroprusside (SNP; 1-5 µg/g in 2-10 µl of saline) immediately followed by an injection of PE (4-20 µg/g in 2-10 µl of saline) in mice anesthetized with pentobarbital sodium. The baroreflex was characterized by analysis of data collected during the PE-induced rise in arterial pressure beginning at the nadir of the SNP-induced fall in pressure.
Afferent baroreceptor sensitivity (n = 5). The afferent component of the baroreceptor reflex was evaluated by recording ADNA during SNP- and PE-induced changes in arterial pressure following the same protocol as described for the baroreflex studies.
Central component of baroreflex (pentobarbital sodium anesthesia, n = 4; ketamine-acepromazine anesthesia, n = 4). The central component of the baroreflex was characterized by measuring the reflex changes in mean arterial pressure and heart rate in response to electrical stimulation of the left ADN. The stimulus was composed of rectangular pulses (10 V, 2-ms duration) delivered at 2, 5, 10, and 15 Hz. Responses to each frequency of stimulation were measured at least twice in each experiment with the order of changes in frequency reversed. Each stimulus period was maintained for 10-20 s with recovery intervals of ~3 to 5 min. The protocol was performed in mice anesthetized with pentobarbital sodium (n = 4) and in a separate group of mice anesthetized with ketamine and acepromazine (n = 4). The stimulation-induced changes in heart rate and arterial pressure were abolished after crushing the ADN cranial to the electrode, confirming that the responses were reflex in nature.
Efferent component of baroreflex control of heart rate (pentobarbital sodium anesthesia, n = 5; ketamine-acepromazine anesthesia, n = 4). The chronotropic responsiveness of the heart to increased vagal efferent activity was evaluated by measuring the heart rate response to electrical stimulation of the peripheral end of the cut right vagus nerve. The nerve was stimulated for periods of 10-20 s with rectangular pulses (10 V, 2-ms duration) of varying frequency (2, 5, 10, and 15 Hz). The protocol was performed in mice anesthetized with pentobarbital sodium (n = 5) and mice anesthetized with ketamine and acepromazine (n = 4).
Data analysis.
The ratemeter output of ADNA and RSNA (spikes/s) was measured manually
from the pen-recorder traces at 0.8-s intervals. Levels of ADNA and
RSNA were normalized as a percentage of the maximum level of activity
recorded during PE and SNP administration, respectively. The
relationship between diastolic arterial pressure and nerve activity was
determined by fitting the data to a sigmoidal logistic function
(28). The logistic function for control of RSNA conformed to the mathematical expression Y = P1/{1+
exp[P2 (X
P3)]} + P4, where X = diastolic arterial pressure,
Y = RSNA (%max), P1 = maximum minimum RSNA (range), P2 = slope coefficient,
P3 = diastolic arterial pressure at 50% of the RSNA
range (Pmid), and P4 = minimum RSNA. The
maximum slope (gain) was calculated as P1 × P2/4. The diastolic threshold (Pth) and
saturation (Psat) pressures were calculated from the third
derivative of the logistic function. The same general equation was used
for analysis of ADNA where Y = ADNA (%max),
P4 = maximum ADNA, and P1 (ADNA range) was
expressed as a negative value. Approximately 15-25 data points
measured over 12-20 s were used to construct the function curves.
Curve parameters for the baroreceptor function curve (diastolic
pressure-ADNA) and the reflex function curve (diastolic pressure-RSNA)
were compared using the unpaired t-test (GB-Stat 6.0 software). Peak changes in mean arterial pressure and heart rate were
measured in response to graded electrical stimulation of baroreceptor
afferents in the ADN and vagal efferent nerves. The effects of
stimulation frequency and anesthesia (pentobarbital sodium vs.
ketamine) were analyzed by ANOVA and Newman-Keuls post hoc test
(GB-Stat 6.0 software). Differences were considered significant when
P < 0.05. Data are presented as means ± SE.
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Baseline arterial pressure and heart rate in anesthetized mice. The baseline level of mean arterial pressure averaged 89 ± 2 and 86 ± 4 mmHg in pentobarbital sodium (n = 10)- and ketamine-acepromazine (n = 6)-anesthetized mice, respectively (P = NS). Baseline heart rate was significantly influenced by the type of anesthesia averaging 514 ± 17 beats/min under pentobarbital sodium anesthesia (n = 10) and 477 ± 9 beats/min under ketamine-acepromazine anesthesia (n = 6).
Baroreflex control of RSNA.
RSNA recorded under baseline conditions exhibited synchronized bursts
of activity as has been observed in other species (7, 13, 29, 42,
46, 48) (Fig. 1B). The baroreflex was characterized by measuring RSNA over a wide range of arterial pressure induced by
intravenous injections of SNP and PE (n = 6). SNP
reduced mean arterial pressure to 47 ± 7 mmHg and increased RSNA.
Subsequent injection of PE produced a ramp increase in mean arterial
pressure reaching a maximum of 160 ± 11 mmHg and inhibited RSNA
(Fig. 2). The RSNA and diastolic arterial
pressure data measured during the ramp increase in pressure were
plotted and fit to a logistic sigmoidal function that defined
baroreflex parameters in each mouse studied (Fig.
3, left). The values of
Pth, Pmid, Psat, range, and maximum
gain of the baroreflex function curve are shown in Table
1.
|
|
|
Afferent component of baroreflex.
The afferent component of the baroreflex was characterized by measuring
ADNA over a wide range of arterial pressure elicited by intravenous
injections of SNP and PE (n = 5). The ADNA occurred in
bursts in phase with the arterial pressure pulse characteristic of
baroreceptor afferents (Fig. 1A), was decreased in response to SNP-induced hypotension, and was increased in response to the PE-induced increase in arterial pressure (Fig.
4). The relationship between ADNA and
diastolic arterial pressure was sigmoidal (Fig. 2, right).
The values of Pth, Pmid, Psat,
range, and maximum gain for the afferent baroreceptor function curve
did not differ significantly from the parameters for the reflex RSNA
function curve (Table 1).
|
Central component of baroreflex.
Electrical stimulation of the ADN evoked frequency-dependent decreases
in arterial pressure and heart rate (Figs.
5 and 6). The magnitude of the reflex decrease in arterial pressure was similar
in pentobarbital sodium (n = 4)- and
ketamine-acepromazine (n = 4)-anesthetized mice (Fig.
6). In contrast, the reflex decrease in heart rate was significant in
ketamine-acepromazine-anesthetized mice but was essentially nonexistent
in pentobarbital sodium-anesthetized mice (Fig. 6).
|
|
Efferent component of baroreflex.
Electrical stimulation of the right vagus nerve evoked
frequency-dependent decreases in heart rate (Fig.
7). The magnitude of the bradycardia was
not significantly different in pentobarbital sodium (n = 5)- vs. ketamine-acepromazine (n = 4)-anesthetized mice (Fig. 7). Thus, pentobarbital sodium nearly
abolished the bradycardic response to ADN stimulation (Fig. 6) without
altering the bradycardic response to stimulation of vagal efferents
(Fig. 7).
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
The present study provides a quantitative assessment of afferent, central, and efferent components of the arterial baroreflex in anesthetized Webster 4 mice. The combination of direct electrophysiological recording of ADNA and RSNA with measurement of cardiovascular responses to electrical stimulation of baroreceptor afferents and vagal efferents provides a powerful approach to localize the site (e.g., afferent, central, or efferent) responsible for changes in reflex function in pathological states and in genetically modified mice. To illustrate the approach, we demonstrated that pentobarbital sodium anesthesia selectively impairs the central mediation of baroreflex control of heart rate in mice. Baroreflex control of RSNA and arterial pressure as well as the chronotropic responsiveness of the heart to vagal efferent activity are relatively preserved during pentobarbital sodium anesthesia in Webster 4 mice.
Baroreflex in mice vs. other species. The baroreceptor reflex has been studied extensively and shown to be of major importance in the regulation of arterial pressure and cardiovascular function in a wide variety of species including humans (3, 39). Recent studies have provided quantitative assessment of baroreflex sensitivity for control of heart rate in conscious and anesthetized mice (25, 30, 32, 34, 38). A few laboratories including our own have recorded RSNA in anesthetized mice (30, 31, 48). The results indicate that baroreflex function is qualitatively similar in mice and other species.
Although differences in methods of analyzing baroreflex function and differences in baseline heart rate and autonomic tone make it difficult to quantitatively compare baroreflex sensitivity between species, some differences are evident. Baroreflex sensitivity for control of heart rate (beats · min
1 · mmHg1)
appears to be higher in mice (25, 30, 32, 34, 38) than in
rats (13, 22, 23, 30, 35). Ling et al. (30) directly compared baroreflex function in urethane-anesthetized mice
(129 Sv/J × ICR strain) and anesthetized Sprague-Dawley rats under similar conditions and observed significantly higher baroreflex sensitivity for control of both heart rate and normalized RSNA in mice.
Our finding of a relatively high baroreflex-RSNA gain in pentobarbital
sodium-anesthetized mice (Webster 4 strain) (2.3 ± 0.5%/mmHg), a
value higher than that observed in anesthetized rats (5, 7,
47), supports the conclusion reached by Ling et al.
(30) that baroreflex sensitivity may be higher in mice. Baroreflex sensitivity appears to be slightly lower in mice and rats
than in rabbits (29, 42, 46). The physiological
significance of differences in baroreflex sensitivity between species
is unclear.
The results discussed in the previous paragraph are based on analysis
of RSNA normalized as a percent change from baseline or a percent of
maximum activity. It is worthwhile to point out the importance of
normalizing measurements of activity recorded from multiple nerve
fibers when comparing results obtained from separate groups of animals.
The absolute level of activity measured in microvolts or spikes per
second is dependent on the recording conditions, the number and size of
the nerve fibers, and the proximity of the active fibers to the
electrode. The reduced number and diameter of sympathetic nerve fibers
innervating target organs, including the kidneys, in mice (8, 10,
40) likely account for the decreased absolute levels of baseline
and maximum RSNA recorded in mice compared with larger species
(20, 21, 30, 31, 33). The method of normalization of nerve
activity is also important; the same RSNA data will translate to
significantly higher values of baroreflex range and gain when RSNA is
expressed as a percent change from baseline than when it is expressed
as a percent of maximum activity.
To our knowledge, this is the first full report of ADNA recording in
mice. We observed a baroreceptor sensitivity of 2.9 ± 0.5%/mmHg
in pentobarbital sodium-anesthetized Webster 4 mice. In a
preliminary report, Moreira et al. (37) reported a gain of
1.67 ± 0.22%/mmHg in pentobarbital sodium-anesthetized DBA/2 mice. It is unclear if the difference in gains in these studies is
significant and whether it may reflect differences in methods and/or a
difference between the two strains of mice. Values of arterial
pressure-ADNA gain range from ~1.2 to 3%/mmHg in rats and rabbits
(7, 15, 17, 36).
Similar to rats, the ADN in mice appears to contain primarily
baroreceptor afferents, with little or no indication of chemoreceptor activity. We observed residual ADNA at low arterial pressure after injection of nitroprusside, but it was unclear whether this activity was baroreceptor or chemoreceptor in nature (Figs. 3 and 4). Electrical stimulation of the ADN always evoked a baroreflex pattern of response (decreased arterial pressure). A chemoreflex pattern of increased pressure was never observed. Biscoe and Pallot (2)
demonstrated that carotid sinus denervation abolishes oxygen-induced
inhibition of ventilation in mice, suggesting that the majority of
chemoreceptor afferents travel in the carotid sinus nerves in mice.
Importance of assessing afferent, central, and efferent baroreflex components. The redundancy in mechanisms regulating arterial pressure and the tremendous capacity of the nervous system to compensate for alterations in function encourage an experimental approach that can independently assess afferent, central, and efferent components of the reflex. For example, previous studies have shown that baroreflex control of sympathetic activity may be preserved despite a significant decrease in baroreceptor afferent sensitivity in hypertension and heart failure (6, 18, 44). Enhanced CNS mediation of the reflex may compensate for decreased baroreceptor sensitivity (6). Alternatively, impaired CNS mediation of the reflex may contribute to reflex dysfunction, for example, in hypertension and with aging (16, 20). The responsiveness of the heart and blood vessels to efferent autonomic outflow is an additional important determinant of baroreflex sensitivity. Changes in end-organ responsiveness may contribute to altered reflex function, or alternatively, may compensate for and obscure an impairment in afferent or central mediation of the reflex. For example, decreased baroreflex control of parasympathetic activity and heart rate is accompanied by an increased heart rate response to vagal efferent nerve activity in hypertension (11) and with aging (12). The ability to separately assess afferent, central, and efferent components of the baroreflex will be particularly important in studies of genetically modified mice where one would expect compensatory changes in function to occur.
To illustrate the usefulness of this approach, we evaluated effects of pentobarbital sodium vs. ketamine anesthesia on central and efferent components of the baroreflex. We found that electrical stimulation of baroreceptor afferents in the ADN evoked reflex decreases in heart rate and arterial pressure in ketamine-anesthetized mice (Figs. 5 and 6). In contrast, the reflex decrease in heart rate was nearly abolished in pentobarbital sodium-anesthetized mice despite preservation of the reflex decrease in arterial pressure (Fig. 6). The results suggest that pentobarbital sodium selectively impairs reflex control of heart rate and does not exert a major effect on reflex control of peripheral sympathetic nerve activity or vascular resistance in mice. The latter suggestion was confirmed by our finding of a high baroreflex-RSNA gain (2.3 ± 0.5%/mmHg) in pentobarbital sodium-anesthetized mice. Impaired heart rate responses to ADN stimulation could conceivably result from an impaired CNS mediation of the reflex and/or a reduced cardiac response to reflex changes in parasympathetic and sympathetic nerve activity. Electrical stimulation of vagal efferents decreased heart rate equivalently in pentobarbital sodium- and ketamine-anesthetized mice (Fig. 7), strongly suggesting that the site of action of pentobarbital sodium was within the CNS. Inhibition of baroreflex control of heart rate by pentobarbital sodium has been demonstrated in other species (23, 41, 43, 45). Ketamine-acepromazine or urethane (30, 38) may be preferable over pentobarbital sodium or inactin (1) as anesthetic agents for studies of reflex control of heart rate in mice. Although barbiturates such as pentobarbital sodium are generally not recommended for studies of heart rate control, they may be appropriate for studies of reflex control of sympathetic nerve activity in both mice (present study) and rats (7). In addition to measuring responses to ADN stimulation, insight into the central mediation of the baroreflex can be gained through measurements of ADNA and sympathetic nerve activity over a range of pressure and analysis of the input-output relationship (4, 6, 7, 24). Although our failure to record ADNA and RSNA simultaneously prevents a precise analysis, the finding of similar pressure thresholds and maximum gains for the afferent and reflex function curves suggests a one-to-one coupling of changes in afferent to efferent nerve activity with a "central gain" close to 1 (change in RSNA/change in ADNA) under the conditions of our experiments. Calculated values of central baroreflex gain in previous studies using this type of analysis have ranged from 0.9 to 2.4 (4, 6, 7). The variability between studies may be attributed, in part, to differences in the number of intact cardiovascular afferents (carotid sinus, aortic depressor, and vagus nerves), in the rapidity and magnitude of changes in pressure used to drive changes in baroreceptor afferent activity, and in factors modulating the central mediation of the reflex. In summary, the results of this study demonstrate the feasibility of assessing afferent, central, and efferent components of the baroreflex in mice. Application of these approaches to genetically modified mice promises to advance our knowledge of the fundamental cellular and molecular mechanisms mediating baroreflex control of the circulation in normal and pathological states.| |
ACKNOWLEDGEMENTS |
|---|
This work was supported by a Veterans Affairs Merit Review Award (to M. W. Chapleau) and funds from National Institutes of Health Grant P-01 HL-14388.
| |
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: M. W. Chapleau, Dept. of Internal Medicine, E327-1 General Hospital, Univ. of Iowa, 200 Hawkins Drive, Iowa City, IA 52242 (E-mail: mark-chapleau{at}uiowa.edu).
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.
July 18, 2002;10.1152/ajpregu.00768.2001
Received 2 January 2001; accepted in final form 17 July 2002.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Ackermann, U,
and
Deliva RD.
Reduced baroreceptor sensitivity during hypotension in ANP-knockout mice.
Can J Physiol Pharmacol
79:
201-205,
2001.
2.
Biscoe, TJ,
and
Pallot DJ.
The carotid body chemoreceptor: an investigation in the mouse.
Q J Exp Physiol
67:
557-576,
1982.
3.
Chapleau, MW,
and
Abboud FM.
Neuro-Cardiovascular Regulation: From Molecules to Man. New York: Ann NY Acad Sci, 2001.
4.
Chapleau, MW,
Hajduczok G,
and
Abboud FM.
Resetting of the arterial baroreflex: peripheral and central mechanisms.
In: Reflex Control of the Circulation, edited by Zucker IH,
and Gilmore JP.. Boca Raton, FL: CRC, 1991, p. 165-194.
5.
Crandall, ME,
and
Heesch CM.
Baroreflex control of sympathetic outflow in pregnant rats: effects of captopril.
Am J Physiol Regul Integr Comp Physiol
258:
R1417-R1423,
1990.
6.
Dibner-Dunlap, ME,
and
Thames MD.
Baroreflex control of renal sympathetic nerve activity is preserved in heart failure despite reduced arterial baroreceptor sensitivity.
Circ Res
65:
1526-1535,
1989.
7.
DiBona, GF,
and
Sawin LL.
Reflex regulation of renal nerve activity in cardiac failure.
Am J Physiol Regul Integr Comp Physiol
266:
R27-R39,
1994.
8.
DiBona, GF,
Sawin LL,
and
Jones SY.
Differentiated sympathetic neural control of the kidney.
Am J Physiol Regul Integr Comp Physiol
271:
R84-R90,
1996.
9.
Drummond, HA,
Price MP,
Welsh MJ,
and
Abboud FM.
A molecular component of the arterial baroreceptor mechanotransducer.
Neuron
21:
1435-1441,
1998.
10.
Fazan VPS, Ma X, Chapleau MW, and Barreira AA. Qualitative and
quantitative morphology of renal nerves in C57BL/6J mice.
Anatomical Record In press.
11.
Ferrari, AU,
Daffonchio A,
Franzelli C,
and
Mancia G.
Cardiac parasympathetic hyperresponsiveness in spontaneously hypertensive rats.
Hypertension
19:
653-657,
1992.
12.
Ferrari, AU,
Daffonchio A,
Gerosa S,
and
Mancia G.
Alterations in cardiac parasympathetic function in aged rats.
Am J Physiol Heart Circ Physiol
260:
H647-H649,
1991.
13.
Francis, J,
Weiss RM,
Wei SG,
Johnson AK,
and
Felder RB.
Progression of heart failure after myocardial infarction in the rat.
Am J Physiol Regul Integr Comp Physiol
281:
R1734-R1745,
2001.
14.
Gassmann, M,
and
Hennet T.
From genetically altered mice to integrative physiology.
News Physiol Sci
13:
53-57,
1998.
15.
Gordon, FJ,
and
Mark AL.
Mechanism of impaired baroreflex control in prehypertensive Dahl salt-sensitive rats.
Circ Res
54:
378-387,
1984.
16.
Guo, GB,
and
Abboud FM.
Impaired central mediation of the arterial baroreflex in chronic renal hypertension.
Am J Physiol Heart Circ Physiol
246:
H720-H727,
1984.
17.
Guo, GB,
Schmid PG,
and
Abboud FM.
Sites at which vasopressin facilitates baroreflex inhibition of lumbar sympathetic nerve activity.
Am J Physiol Heart Circ Physiol
251:
H644-H655,
1986.
18.
Guo, GB,
and
Thames MD.
Abnormal baroreflex control in renal hypertension is due to abnormal baroreceptors.
Am J Physiol Heart Circ Physiol
245:
H420-H428,
1983.
19.
Guo, GB,
Thames MD,
and
Abboud FM.
Arterial baroreflexes in renal hypertensive rabbits. Selectivity and redundancy of baroreceptor influence on heart rate, vascular resistance, and lumbar sympathetic nerve activity.
Circ Res
53:
223-234,
1983.
20.
Hajduczok, G,
Chapleau MW,
and
Abboud FM.
Rapid adaptation of central pathways explains the suppressed baroreflex with aging.
Neurobiol Aging
12:
601-604,
1991.
21.
Hajduczok, G,
Chapleau MW,
Johnson SL,
and
Abboud FM.
Increase in sympathetic activity with age. I. Role of impairment of arterial baroreflexes.
Am J Physiol Heart Circ Physiol
260:
H1113-H1120,
1991.
22.
Head, GA,
and
McCarty R.
Vagal and sympathetic components of the heart rate range and gain of the baroreceptor-heart rate reflex in conscious rats.
J Auton Nerv Syst
21:
203-213,
1987.
23.
Howe, PR,
Rogers PF,
and
Head GA.
Limited baroreflex control of heart rate in young stroke-prone spontaneously hypertensive rats.
J Hypertens
7:
69-75,
1989.
24.
Imaizumi, T,
Harasawa Y,
Ando SI,
Sugimachi M,
and
Takeshita A.
Transfer function analysis from arterial baroreceptor afferent activity to renal nerve activity in rabbits.
Am J Physiol Heart Circ Physiol
266:
H36-H42,
1994.
25.
Ishii, T,
Kuwaki T,
Masuda Y,
and
Fukuda Y.
Postnatal development of blood pressure and baroreflex in mice.
Auton Neurosci
94:
34-41,
2001.
26.
James, JF,
Hewett TE,
and
Robbins J.
Cardiac physiology in transgenic mice.
Circ Res
82:
407-415,
1998.
27.
Just, A,
Faulhaber J,
and
Ehmke H.
Autonomic cardiovascular control in conscious mice.
Am J Physiol Regul Integr Comp Physiol
279:
R2214-R2221,
2000.
28.
Kent, BB,
Drane JW,
Blumenstein B,
and
Manning JW.
A mathematical model to assess changes in the baroreceptor reflex.
Cardiology
57:
295-310,
1972.
29.
Kumagai, H,
Suzuki H,
Ryuzaki M,
Matsukawa S,
and
Saruta T.
Baroreflex control of renal sympathetic nerve activity is potentiated at early phase of two-kidney, one-clip Goldblatt hypertension in conscious rabbits.
Circ Res
67:
1309-1322,
1990.
30.
Ling, GY,
Cao WH,
Onodera M,
Ju KH,
Kurihara H,
Kurihara Y,
Yazaki Y,
Kumada M,
Fukuda Y,
and
Kuwaki T.
Renal sympathetic nerve activity in mice: comparison between mice and rats and between normal and endothelin-1 deficient mice.
Brain Res
808:
238-249,
1998.
31.
Ma, X,
Abboud FM,
and
Chapleau MW.
A novel effect of angiotensin on renal sympathetic nerve activity in mice.
J Hypertens
19:
609-618,
2001.
32.
Madeddu, P,
Salis MB,
and
Emanueli C.
Altered baroreflex control of heart rate in bradykinin B2-receptor knockout mice.
Immunopharmacology
45:
21-27,
1999.
33.
McDowell, TS,
Hajduczok G,
Abboud FM,
and
Chapleau MW.
Baroreflex dysfunction in diabetes mellitus. II. Site of baroreflex impairment in diabetic rabbits.
Am J Physiol Heart Circ Physiol
266:
H244-H249,
1994.
34.
Merrill, DC,
Thompson MW,
Carney CL,
Granwehr BP,
Schlager G,
Robillard JE,
and
Sigmund CD.
Chronic hypertension and altered baroreflex responses in transgenic mice containing the human renin and human angiotensinogen genes.
J Clin Invest
97:
1047-1055,
1996.
35.
Meyrelles, SS,
Mill JG,
Cabral AM,
and
Vasquez EC.
Cardiac baroreflex properties in myocardial infarcted rats.
J Auton Nerv Syst
60:
163-168,
1996.
36.
Moreira, ED,
Ida F,
Oliveira VL,
and
Krieger EM.
Early depression of the baroreceptor sensitivity during onset of hypertension.
Hypertension
19, SupplII:
II198-II201,
1992.
37.
Moreira, ED,
Pires MD,
Koike MK,
Ida F,
Krieger JE,
and
Krieger EM.
Baroreceptor function in mice (Abstract).
Hypertension
29:
861,
1997.
38.
Peotta, VA,
Vasquez EC,
and
Meyrelles SS.
Cardiovascular neural reflexes in L-NAME-induced hypertension in mice.
Hypertension
38:
555-559,
2001.
39.
Persson, PB,
and
Kirchheim HR.
Baroreceptor Reflexes: Integrative Functions and Clinical Aspects. Berlin: Springer-Verlag, 1991.
40.
Purves, D,
Rubin E,
Snider WD,
and
Lichtman J.
Relation of animal size to convergence, divergence, and neuronal number in peripheral sympathetic pathways.
J Neurosci
6:
158-163,
1986.
41.
Stornetta, RL,
Guyenet PG,
and
McCarty RC.
Autonomic nervous system control of heart rate during baroreceptor activation in conscious and anesthetized rats.
J Auton Nerv Syst
20:
121-127,
1987.
42.
Undesser, KP,
Trapani AJ,
Morgan WW,
and
Bishop VS.
Role of central catecholamines on the potentiation of the baroreflex produced with vasopressin. A study using 6-hydroxydopamine.
Circ Res
58:
882-889,
1986.
43.
Vatner, SF,
Franklin D,
and
Braunwald E.
Effects of anesthesia and sleep on circulatory response to carotid sinus nerve stimulation.
Am J Physiol
220:
1249-1255,
1971.
44.
Wang, W,
Chen JS,
and
Zucker IH.
Carotid sinus baroreceptor reflex in dogs with experimental heart failure.
Circ Res
68:
1294-1301,
1991.
45.
Watkins, L,
and
Maixner W.
The effect of pentobarbital anesthesia on the autonomic nervous system control of heart rate during baroreceptor activation.
J Auton Nerv Syst
36:
107-114,
1991.
46.
Weinstock, M,
Korner PI,
Head GA,
and
Dorward PK.
Differentiation of cardiac baroreflex properties by cuff and drug methods in two rabbit strains.
Am J Physiol Regul Integr Comp Physiol
255:
R654-R664,
1988.
47.
Whitescarver, SA,
Roberts AM,
Stremel RW,
Jimenez AE,
and
Passmore JC.
Nicotine impairs reflex renal nerve and respiratory activity in deoxycorticosterone acetate-salt rats.
Hypertension
17:
179-186,
1991.
48.
Zhang, W,
Li JL,
Hosaka M,
Janz R,
Shelton JM,
Albright GM,
Richardson JA,
Südhof TC,
and
Victor RG.
Cyclosporine A-induced hypertension involves synapsin in renal sensory nerve endings.
Proc Natl Acad Sci USA
97:
9765-9770,
2000.
This article has been cited by other articles:
|
|
 |
|
  B. E. Hunt, R. Tamisier, G. S. Gilmartin, M. Curley, A. Anand, and J. W. Weiss Baroreflex responsiveness during ventilatory acclimatization in humans Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1794 - H1801. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Shi, F. A. Schaller, N. Tierney, P. Chanthavong, S. Chen, P. B. Raven, and M. L. Smith Physically Active Lifestyle Enhances Vagal-Cardiac Function but Not Central Autonomic Neural Interaction in Elderly Humans Experimental Biology and Medicine, February 1, 2008; 233(2): 209 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Gu, M. Lin, J. Liu, D. Gozal, K. E. Scrogin, R. Wurster, M. W. Chapleau, X. Ma, and Z. Cheng Selective impairment of central mediation of baroreflex in anesthetized young adult Fischer 344 rats after chronic intermittent hypoxia Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2809 - H2818. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yu, Z.-H. Zhang, S.-G. Wei, Y. Chu, R. M. Weiss, D. D. Heistad, and R. B. Felder Central Gene Transfer of Interleukin-10 Reduces Hypothalamic Inflammation and Evidence of Heart Failure in Rats After Myocardial Infarction Circ. Res., August 3, 2007; 101(3): 304 - 312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lin, R. Liu, D. Gozal, W. B. Wead, M. W. Chapleau, R. Wurster, and Z. Cheng Chronic intermittent hypoxia impairs baroreflex control of heart rate but enhances heart rate responses to vagal efferent stimulation in anesthetized mice Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H997 - H1006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Fazan Jr., M. de Oliveira, V. J. Dias da Silva, L. F. Joaquim, N. Montano, A. Porta, M. W. Chapleau, and H. C. Salgado Frequency-dependent baroreflex modulation of blood pressure and heart rate variability in conscious mice Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1968 - H1975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Jung, R. Harrison, K. H. Lee, J. Genut, D. Nyhan, E. M. Brooks-Asplund, A. A. Shoukas, J. M. Hare, and D. E. Berkowitz Simulated microgravity produces attenuated baroreflex-mediated pressor, chronotropic, and inotropic responses in mice Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H600 - H607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Townsend, A. S. Jung, Y. S. G. Hoe, R. Y. Lefkowitz, S. A. Khan, C. A. Lemmon, R. W. Harrison, K. Lee, L. A. Barouch, S. Cotecchia, et al. Critical Role for the {alpha}-1B Adrenergic Receptor at the Sympathetic Neuroeffector Junction Hypertension, November 1, 2004; 44(5): 776 - 782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. B. Persson and J. A. Armour Dual vagal cardiac efferent pathways Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2004; 286(4): R624 - R624. [Full Text] [PDF]
|
|
|
|
|
|
R. L. Davisson Physiological genomic analysis of the brain renin-angiotensin system Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2003; 285(3): R498 - R511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ehmke Mouse gene targeting in cardiovascular physiology Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2003; 284(1): R28 - R30. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
Significant difference of
responses in ketamine-acepromazine- vs. pentobarbital
sodium-anesthetized mice, P < 0.05. Baseline arterial
pressure averaged 88 ± 1 and 86 ± 4 mmHg in pentobarbital
sodium- and ketamine-acepromazine-anesthetized mice, respectively.
Corresponding measurements of baseline HR averaged 519 ± 26 and
477 ± 9 beats/min in the 2 groups of mice.
