(Hypertension. 1999;34:247-252.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Effect of Magnesium Deficiency on Autonomic Circulatory Regulation in Conscious Rats
From the Departments of Systems Physiology (Y.M., Y. Harada, Y. Hayashida), Health Development (M.I.), and Internal Medicine (Y.N.), University of Occupational and Environmental Health, Kitakyushu, Japan.
Correspondence to Yoshinobu Murasato, MD, PhD, Department of Systems Physiology, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi, Kitakyushu 807-8555, Japan. E-mail murasato{at}med.uoeh-u.ac.jp
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Abstract |
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Abstract—A close relationship between magnesium and cardiovascular function has been reported; however, the effect of magnesium deficiency on autonomic cardiovascular regulation has not been clarified. We investigated the effect of magnesium deficiency on the autonomic regulation of oscillations of the R-R interval, arterial blood pressure (BP), and renal sympathetic nerve activity (RSNA) by using the maximum entropy method in conscious rats. Its effect on baroreflex control of RSNA and heart rate were also investigated with a logistic function curve. Mean BP in magnesium-deficient rats was higher than that in control rats (mean±SE, 114.0±4.3 versus 101.6±3.4 mm Hg; P<0.05), and urinary excretion of catecholamine was increased by 2.4-fold. The fraction of low-frequency oscillation of RSNA was reduced (31.7±0.9% versus 36.2±1.5%, P<0.05) and the correlation between low-frequency oscillations of BP and RSNA was weakened in magnesium-deficient rats. There was no difference in high-frequency oscillation of the R-R interval, which is related to vagal tone, whereas sympathetic tone became dominant (square root of low-frequency/high-frequency ratio of R-R interval, 1.00±0.05 versus 0.67±0.05, P<0.0001) in magnesium-deficient rats. The maximal gain in the BP-RSNA relation tended to be reduced in magnesium-deficient rats (-7.7±1.1% versus -12.2±1.9%/mm Hg, P=0.07); however, that in the BP–heart rate relation was increased (-8.1±0.7 versus -4.5±0.5 bpm/mm Hg, P<0.01). These results suggest that magnesium deficiency induces sympathetic excitation, which results in hypertension but attenuates the baroreflex-related response of sympathetic nerves, whereas magnesium deficiency enhances the sensitivity of the sinus node to autonomic regulation.
Key Words: magnesium deficiency • baroreflex • sympathetic nerve • autonomic nervous system • spectral analysis
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Introduction |
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Magnesium (Mg) is an essential element of circulatory regulation and is the most common intracellular cation after potassium.1 2 3 It has been reported that Mg plays a role in numerous enzymatic processes in the cardiovascular system, such as in kinases, cyclases, and adenosine triphosphatase or guanine triphosphatase,2 and is a naturally occurring antagonist to calcium.4 Thus, Mg affects the pivotal cardiac functions, including cardiac contraction,5 beating rhythm,5 6 vasomotor control,4 7 8 9 10 and proliferation of smooth muscle cells in vessels.9 11 Mg deficiency contributes to the pathogenesis of several cardiovascular diseases, eg, hypertension,12 vasospastic angina,13 ventricular arrhythmia,14 and mitral valve prolapse.15
Recently, Fiset et al16 reported a high incidence of sudden death in Mg-deficient rats, and this result is consistent with epidemiological reports of a high incidence of sudden death in areas with low levels of Mg in drinking water17 and also with clinical reports that hypomagnesemia is frequently observed in patients with heart failure in whom sudden death occurs.14 18 Animal studies have suggested that there are 2 mechanisms of sudden death related to Mg deficiency: arrhythmogenesis and coronary vasospasm.1 4 5 19 Moreover, the effect of Mg deficiency on the autonomic nervous system may act as a neurogenic trigger of a fatal event. Fiset et al16 reported that fatal arrhythmia occurred after seizures in Mg-deficient rats, whereas there was a small effect on repolarization of ventricular myocytes. The authors implied that the abnormal response of the autonomic nervous system to auditory stress led to a fatal event.
To assess autonomic nervous activity, oscillations of the R-R interval (RRI) and blood pressure (BP) have generally been investigated by spectral analysis.20 21 22 23 24 25 26 27 28 These oscillations consist of high-frequency (HF), low-frequency (LF), and very-low-frequency components. The HF component of RRI variability is believed to be mediated by cardiac parasympathetic tone, whereas the LF component is mediated by both cardiac sympathetic and parasympathetic tones, which are regulated by the baroreflex. Hence, the ratio of LF power to HF power (LF/HF) is an index of cardiac sympathovagal balance.20 24 26 The LF component of BP variability parallels baroreflex-related sympathetic nerve activity.21 26 27 It has also been reported that the baroreflex is a sensitive marker of sudden death and malignant ventricular arrhythmia.29
However, the effect of Mg deficiency on the autonomic nervous system has not been clarified. In this study, we investigated the effect of Mg deficiency on the autonomic regulation of oscillations of RRI, BP, and renal sympathetic nerve activity (RSNA) using the maximum entropy method. Next, the correlations between baroreflex-related parameters and the LF component of RSNA variability were investigated. Finally, we investigated the changes in RSNA and heart rate (HR) in response to changes in BP induced by drug administration and analyzed the effect of Mg deficiency on baroreflex sensitivity.
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Methods |
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Animals and Diets
This study was performed in accordance with the guidelines specified for institutional animal care and use of the University of Occupational and Environmental Health, Kitakyushu, Japan.
Seventeen male Wistar rats, weighing 180 to 200 g, were housed in
stainless-steel cages with a constant temperature (24°C), constant
humidity (55%), and a daily 12-hour light/dark cycle. They were
divided into 2 groups, the control group (n=8), and Mg-deficient (MGD)
group (n=9), and fed a synthetic diet (Oriental Kobo) that contained
either 3.79 mmol Mg/100 g (control diet) or 0.19 mmol Mg/100
g (MGD diet). The composition of the 2 diets were the same except for
the amount of Mg. The MGD diet contained 39.7% corn starch, 20.0%
casein, 13.2% 
-corn starch, 10.0% sucrose, 7.0% soybean oil,
5.0% cellulose, 3.5% mineral mixture, 1.0% vitamin mixture, 0.3%
L-cystein, and 0.3% choline bitartrate. All rats were
given deionized water.
Urine Sampling
At 3 weeks of dietary treatment, each rat was weighed and placed
in another cage so that a 24-hour urine sample could be collected.
Urine was collected for individual rats, and Na, K, and Cl were
measured with an autoanalyzer (Hitachi 7170, Hitachi
Seisakusho). Mg and Ca were measured with a spectrophotometer (Hitachi
Z-6100, Hitachi Seisakusho). Adrenaline and noradrenaline
were measured by high-performance liquid
chromatography (HPLC-725CA, Tosoh). The nitrate plus
nitrite (NOx) concentration was determined with an autoanalyzer
(TCL-NOx 1000, Tokyo Kasei Kogyo). The neutralized supernatant was
passed through a copper-coated cadmium column to reduce nitrate to
nitrite and then reacted with Griess reagents. Absorbance at 540 nm,
which represents the total amount of NOx, was measured.
Animal Preparation and Data Recording
Two or 3 days after they were returned to their home cages, the
rats were anesthetized with pentobarbital (50 mg/kg IP) and
prepared for recording of arterial BP, ECG, and
RSNA. The procedure has been described
elsewhere.24 30 In brief, stainless-steel, hooked bipolar
electrodes were placed around a left renal sympathetic nerve, and ECG
electrodes were implanted at midchest. Polyethylene catheters were
inserted via the femoral artery into the lower abdominal aorta and via
the femoral vein into the inferior vena cava. All
recordings were clear enough to be analyzed in 7 rats
in each group.
At least 48 hours after implantation of the electrodes and catheters, an unrestrained rat was placed in its home cage. BP and ECG were amplified and filtered. The fast peaks of R waves on the ECG were detected, and HR was measured. The original RSNA was amplified and filtered (50 to 1000 Hz) by a differential low-noise amplifier, and the rectified signal with a time constant of 0.1 second was then integrated. After the experiment, maximal inhibition of RSNA was induced by intravenous injection of phenylephrine (4 to 10 µg/kg), and background noise was determined. Background noise was subtracted from the data of integrated RSNA during the experiment. For later analysis, analog outputs of BP, HR, ECG, and RSNA were recorded on a digital tape recorder.
Spectral Analysis
Data sampling and spectral analysis were performed by
use of a modification of the method described
previously.24 The RRI, BP, and RSNA waveforms were
replayed, and 210-second sections consisting of consecutive sinus beats
were selected during the control periods. These sections were digitally
sampled by an analog-to-digital converter every 30 ms, and RRI, BP, and
RSNA were analyzed and stored on a microcomputer. Ten data sets
of 1000 points that overlapped one-third of the preceding data set were
processed on a computer system. The time series of data were
analyzed by the maximal entropy method with high resolution
(MemCalc, Suwa Trust).
The magnitude of power was integrated in each band and then averaged within the group. The very-low-frequency band ranged between 0.034 and 0.27 Hz; the LF band, between 0.27 and 0.75 Hz; and the HF band, between 0.75 and 3.5 Hz.24 Each LF power and its square root, LF1/2, of BP and RRI variabilities and the normalized unit of LF power of RSNA variability were investigated to evaluate the baroreflex, where the normalized unit represents the valued power as a percentage of the total power. Because the voltages of RSNA showed a wide range (20 to 200 µV), it is not appropriate to compare the absolute power of RSNA variability. HF power and its square root, HF1/2, of RRI variability were assessed to evaluate parasympathetic nerve activity. LF/HF and its square root, (LF/HF)1/2, of RRI variability were assessed to evaluate sympathovagal balance.
Analysis of Baroreflex Function
The analysis was performed by use of a modification of a
method described in a previous report.30 After the control
period, the mean RSNA, BP, and HR were simultaneously
converted into digital data every 2 ms. These digital values were
averaged every 1 second and stored on a computer (DOS/V machine,
software; Visual Designer, Intelligent Instrumentation). The
relationship between mean BP (MBP) and RSNA and that between MBP and HR
were investigated when BP was increased and decreased by alternating
intravenous injections of phenylephrine (20
µg/kg) and nitroprusside (20 µg/kg) using a syringe pump (CFV-2100,
Nihon Kohden) at a rate of 5 µL/s. The interval between
administration of phenylephrine and nitroprusside was at
least 10 minutes, during which MBP, HR, and RSNA returned to the
baseline levels. To quantify the RSNA response, percentage changes in
the integrated RSNA during the experiment were calculated, taking the
mean value before drug administration as 100%. Data for the MBP-RSNA
and MBP-HR relations after phenylephrine and nitroprusside
administration were fitted to a logistic functional curve with a
logistic equation31 : RSNA or
HR=P4+P1/{1+exp[P2(MBP-P3)]}, where P1 is the range of
RSNA or HR (maximum value-minimum value), P2 is the slope coefficient,
P3 is MBP at the midrange of the curve, and P4 is the minimum RSNA or
HR. Baroreflex sensitivity was defined as the maximum gain of the
logistic function curve. The maximum gain was calculated as
-P1xP2x1/4.
Blood Sampling
At least 24 hours later, blood samples were obtained with an
arterial catheter. Plasma electrolytes (Mg, Ca, Na, K, and
Cl), blood urea nitrogen (BUN), and creatinine were
measured with an autoanalyzer (Hitachi 7170, Hitachi
Seisakusho). One rat, which had a BUN concentration of >21.4
mmol/L and a Mg concentration of 0.83 mmol/L, was excluded from
the MGD group because of dehydration.
Statistical Analysis
All values are mean±SE. Statistical analysis was
performed with StatView software (Abacus Concepts). Comparisons between
the 2 groups were analyzed with an unpaired Student
t test. Correlation coefficients were calculated and tested
using Fisher's z transformation. Significance was
established at P<0.05.
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Results |
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Baseline Characteristics
After 2 weeks, rats in the MGD group began to exhibit signs of hyperactivity, irritability, and a skin rash on the neck and face where their fur fell out. As shown in Table 1, growth retardation was observed in the MGD group. Baseline MBP in the MGD group was greater than that in the control group. There was no difference in mean HR. There was no difference in mean voltage of RSNA (control, 60.0±20.2 µV; MGD, 77.1±22.9 µV), and this value covered a wide range in both groups (control, 30 to 180 µV; MGD, 20 to 200 µV) because of variations in the thickness of the hooked nerve, tissue damage, and nerve-electrode contact. Thus, it is accepted that the voltage of RSNA does not reflect basal sympathetic tone.32
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Neurohumoral factors, NOx, and electrolytes in urine are shown as the amount excreted per kilogram of body weight in Table 1. Excretions of adrenaline and noradrenaline in the MGD group were 2.4-fold greater than those in the control group. NOx was also greater in the MGD group. Mg and Ca in urine were markedly decreased in the MGD group, but there was no difference between groups in Na, K, or Cl.
The results of a biological examination of plasma are also given in Table 1. Serum Mg and Ca concentrations were decreased in the MGD group. There was no difference between the 2 groups in BUN, creatinine, Na, K, or Cl.
Spectral Analysis
Table 2 shows the mean and SE
of parameters that reflect autonomic nervous activity in 70
data sets for each group. There was no difference in LF power or
LF1/2 of BP and RRI variabilities, whereas the
normalized unit value of LF power of RSNA variability decreased in MGD
group. There was no difference in HF power and
HF1/2, which are related to vagal activity. Both
LF/HF and (LF/HF)1/2 were increased in the MGD
group, and the P value for (LF/HF)1/2
was less than that for LF/HF.
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As shown in Figure 1a, there was a positive correlation between LF1/2 of BP variability and the normalized unit value of LF power of RSNA variability in each group (control, r=0.80, P<0.0001; MGD, r=0.41, P=0.0004). However, the r value and its significance in the MGD group were less than those in the control group. As shown in Figure 1b, there was no correlation between the normalized unit value of LF power of RSNA variability and LF1/2 of RRI variability. As shown in Figure 1c, there was a positive correlation between the normalized unit value of LF power of RSNA variability and (LF/HF)1/2 of RRI variability in the MGD group (r=0.44, P=0.0001), whereas there was no correlation in the control group, in which (LF/HF)1/2 of RRI variability remained <1.6.
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Analysis of Baroreflex Function
MBP-RSNA Relation
The means and SEs of the 4 parameters of the
logistic function curve are given in Figure 2a. There was a decrease in P1 and an
increase in P3 in the MGD group. The maximal gain in the MGD group was
smaller than that in the control group, but this difference was not
statistically significant (MGD, -7.7±1.1%/mm Hg; control,
-12.2±1.9%/mm Hg, P=0.07). Figure 2b shows the
correlation curve derived from mean parameters P1 through
P4. The curve in the MGD group shifted to the right (white arrow), and
the range of RSNA was lower (black arrow) in the MGD group than in the
control group.
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MBP-HR Relation
The means and SEs of the 4 parameters are given in
Figure 2c. Both P2 and maximal gain were increased in the MGD
group. Figure 2d shows the correlation curve derived from mean
parameters P1 through P4; note that the slope of the curve
in the MGD group increased (white arrow).
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Discussion |
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The most important finding of this study is that Mg deficiency causes discrepant baroreflex gains for sympathetic nerve activity and HR, ie, attenuation of RSNA and enhancement of HR. The spectral analysis revealed a decrease of the LF component of RSNA variability and loss of correlation between LF components of BP and RSNA variabilities in the MGD group. The blunted baroreflex control of sympathetic nerve activity might be caused by the diminished oscillatory capability of the sympathetic neural modulation under sympathetic overactivity. RRI variability exhibited a sympathetic dominance in proportion to the increase in the LF component of RSNA variability in the MGD group, suggesting an enhancement of the sensitivity of sinus node to sympathetic nerve activity.
Neurohumoral Factors and NO Release
Catecholamine secretion was increased in the MGD
group (Table 1). This is consistent with previous
reports that Mg deficiency caused an increase in
noradrenaline release because of the increased level of
serotonin33 and the increased uptake of
catecholamine at the terminal of the sympathetic
nerves.34 Clinically, hypomagnesemia and over-release of
catecholamine are observed in patients with mitral valve
prolapse, and catecholamine release is improved by Mg
supplementation.15 Mg deficiency induces hyperactivity,
irritability, growth retardation, and skin lesions with
itching,16 all of which were observed in this study. These
stressful conditions may also lead to a secondary increase in
catecholamine secretion.
The lack of a difference in the serum level or excretion of Na and K (Table 1) suggests that the Na/K exchange system in the kidney, including the renin-angiotensin-aldosterone system, was maintained within the normal level in the MGD group. This is consistent with previous findings in Mg-deficient rats.10 However, it has been clinically observed that plasma renin activity was enhanced in hypertensive patients with low serum Mg.12 It has also been reported that hypokalemia often occurs in patients with moderate to severe Mg deficiency and that K is not repleted until Mg is administered concomitantly with K.2 In this study, hypocalcemia was observed concomitantly with hypomagnesemia (Table 1). Mg deficiency leads to secondary hypoparathyroidism because Mg is a cofactor of adenylate cyclase, which produces cAMP, which in turn is required for the exocytosis of parathyroid hormone.35
NO release was enhanced in the MGD group (Table 1). Mak et al36 also showed NO overproduction during Mg deficiency and that it participated in oxidative depletion of red blood cell glutathione. Because we did not evaluate the response of endothelium-derived NO but rather the total amount of NO release in this study, the induction of inducible NO synthase in multiple skin lesions may have caused the increase in NOx. It has been reported that endothelium-dependent vasodilatation induced by acetylcholine is attenuated in the isolated artery of Mg-deficient animals.8 Because the present and previous results36 indicate that Mg deficiency does not impair NO synthesis, atherosclerotic change induced by Mg deficiency might attenuate the response of endothelium-derived NO to shear stress.
The present result that Mg-deficient rats exhibited hypertension coincides with results reported by Altura et al7 but not with results of a study that showed no effect on BP.9 This discrepancy may be due to differences in methodology. In the latter report, the researchers used the tail-cuff method, which requires that the rats be restrained. The measured BP may be influenced by the stress induced by restraint. On the other hand, intraarterial pressure was measured directly with rats in an anesthetized state by Altura et al7 and with rats in a conscious, unrestrained state in this study. The present study also showed that hypertension in Mg-deficient rats was not due to either the enhanced renin-angiotensin system or impairment of NO release but probably to excessive catecholamine release and an abnormal response of vessels to catecholamine.
Baroreflex
It has been reported that the LF oscillations of BP
and RRI increase when sympathetic activity rises,20 27
such as with vasodilatation,25 26 tilting,26
and mental stress,26 and that LF oscillation
of muscle sympathetic nerve activity increases when nitroprusside is
administered in healthy human subjects.26 However, the
present study showed that Mg deficiency increased
catecholamine release (Table 1) but reduced LF
oscillation in RSNA variability (Table 2) and
weakened the correlation between LF oscillation in BP
variability and in RSNA variability (Figure 1a). These results
indicate that the high sympathetic drive caused by Mg deficiency
blunted the baroreflex-related sympathetic oscillation in
response to BP oscillation. This coincides with a report
that LF oscillation of muscle sympathetic nerve activity
was absent in patients with severe heart failure, who had high
sympathetic tone.28 The blunted baroreflex-related
response of RSNA strongly suggested that the sympathetic excitation
caused by Mg deficiency was so tonic that it impaired LF
oscillation. Another possible mechanism may include the
central effect of excessive catecholamine release.
These results obtained by spectral analysis also coincide with results of direct evaluation of the MBP-RSNA relation, ie, Mg deficiency caused a decrease in the range of RSNA, whereas maximal gain tended to decrease (Figure 2a and 2b). This indicates that sympathetic excitation was saturated because it reached its ceiling and reduced its LF oscillation in MGD group. Blunted baroreflex sensitivity in the MBP-RSNA relation has been reported under high sympathetic tone, such as in heart failure32 37 38 and in hypertensive animals.38 Blockade of angiotensin II receptor32 38 or brain ouabain37 prevented impairment of the baroreflex in heart failure. Hirakawa et al30 showed that both RSNA and baroreflex sensitivity increased in proportion to arterial CO2 during hypoxia, suggesting an interaction between the baroreflex and chemoreflex. Although there is no report available concerning the effect of Mg deficiency on brain ouabain, angiotensin, or the interaction between the baroreflex and chemoreflex, excessive catecholamine release might influence them centrally.
Mg deficiency did not significantly affect LF power of BP or RRI
variability (Table 2). Akselrod et al20 reported a
decrease in LF oscillation of BP in spontaneously
hypertensive rats, which have high sympathetic tone, and suggested the
saturation of -receptors. LF oscillation of RRI was
decreased in patients with heart failure,23 and the
mechanism was thought to be limitation of the sinus node responsiveness
to high sympathetic drive22 and ß-receptor
downregulation.39 Because Mg deficiency increased calcium
influx into myocytes3 5 and vascular smooth muscle
cells3 7 and enhanced the responsiveness to sympathetic
excitation,3 19 LF oscillations of BP and RRI
were maintained regardless of the low LF oscillation of
sympathetic activity in this study.
The present results obtained by direct evaluation of the MBP-HR relation also showed that Mg deficiency caused an increase in maximal gain (Figure 2c and 2d), which is opposite of the results obtained for the MBP-RSNA relation (Figure 2a and 2b). This suggests that the responsiveness of the sinus node to autonomic regulation is enhanced despite the blunted response of sympathetic activity to a change in BP. One possible mechanism is that the increased calcium influx caused by Mg deficiency may lead to partial depolarization, enhanced automaticity, or increased sensitivity to catecholamine in the sinus node. Another mechanism may be the result of a modification of Na/K adenosine triphosphatase, whose cofactor is Mg. Thus, this may lead to an increase in intracellular sodium and thereby calcium by Na/Ca exchange.2 19 This suggests arrhythmogenic vulnerability in response to sympathetic excitation during Mg deficiency.2 19
Sympathovagal Balance
With regard to RRI variability, the parameters that
represented the sympathovagal balance were increased in the
MGD group, whereas there was no difference in vagus nerve–related
parameters between the 2 groups (Table 2). This
suggests that sympathetic tone is elevated, because there was no change
in vagal tone. We previously demonstrated that LF/HF decreased despite
sympathetic excitation when both sympathetic and vagus nerves were
activated during hypercapnic hypoxia.24
Thus, LF/HF does not always represent sympathetic tone but
rather sympathovagal balance.
There was no correlation between LF1/2 of RRI variability and sympathetic tone in either group (Figure 1b), and the sympathovagal balance was maintained and independent of sympathetic tone in the control group (Figure 1c). Pagani et al26 reported that there was a close correlation between the normalized unit value of the LF component in the variability of muscle sympathetic nerve activity and LF/HF or LF power of RRI variability in healthy human subjects. The difference between our results in the control group and theirs may be due to the fact that we examined the spontaneous oscillation of sympathetic tone for 30 seconds, whereas they studied the oscillation of 512 beats, probably for >5 minutes, induced by drug administration.26 Another explanation is the difference in cardiac innervation between species, because rats have a HR that is 5-fold higher than that in humans.
In the MGD group, the dominance of sympathetic tone was augmented in proportion to sympathetic excitation (Figure 1c). This suggests that the short-term stability of the sympathovagal balance was impaired by Mg deficiency. This may contribute to the increased gain in the MBP-HR relation.
In summary, Mg deficiency induces excessive catecholamine release and results in hypertension. High sympathetic tone induced by Mg deficiency impairs baroreflex control of sympathetic nerve and reduces its baroreflex-related oscillation. Mg deficiency augments baroreflex control of HR, suggesting a modulatory effect on the sinus node. The results suggest that Mg deficiency leads to a blunted baroreflex and enhances HR response to the stress.
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Acknowledgments |
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This work was supported in part by a Grant-in-Aid for Scientific Research (09770047) from the Ministry of Education, Science, Sports, and Culture of Japan (1997) and by a research grant from the University of Occupational and Environmental Health (1997). The authors thank Katsura Haraguchi for her assistance with the experiment.
Received February 2, 1999; first decision March 15, 1999; accepted April 19, 1999.
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References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Eisenberg MJ. Magnesium deficiency and sudden death. Am Heart J. 1992;124:544–549.[Medline] [Order article via Infotrieve]
2. Rude RK. Physiology of magnesium metabolism and the important role of magnesium in potassium deficiency. Am J Cardiol. 1989;63:31G–34G.[Medline] [Order article via Infotrieve]
3. Seelig M. Cardiovascular consequences of magnesium deficiency and loss: pathogenesis, prevalence and manifestations: magnesium and chloride loss in refractory potassium repletion. Am J Cardiol. 1989;63:4G–21G.[Medline] [Order article via Infotrieve]
4.
Turlapaty PDMVJ, Altura BM. Magnesium deficiency
produces spasms of coronary arteries: relationship to etiology
of sudden death ischemic heart disease. Science. 1980;208:198–200.
5.
Agus ZA, Kelepousis E, Dukes I, Morad M. Cytosolic
magnesium modulates calcium channel activity in mammalian
ventricular cells. Am J Physiol. 1989;256:C452–C455.
6.
Bailie DS, Inoue H, Kaseda S, Ben-David J, Zipes
DP. Magnesium suppression of early afterdepolarizations and
ventricular tachyarrhythmias induced by
cesium in dogs. Circulation. 1988;77:1395–1402.
7.
Altura BM, Altura BT, Gebrewald A, Ising H, Gunter T.
Magnesium deficiency and hypertension: correlation between
magnesium-deficient diets and microcirculatory changes in situ.
Science. 1984;223:1315–1317.
8. Altura BT, Altura BM. Endothelium-dependent relaxation in coronary arteries requires magnesium ions. Br J Pharmacol. 1987;91:449–451.[Medline] [Order article via Infotrieve]
9. Luthringer C, Rayssiguier Y, Gueux E, Berthelot A. Effect of moderate magnesium deficiency on serum lipids, blood pressure and cardiovascular reactivity in normotensive rats. Br J Nutr. 1988;59:243–250.[Medline] [Order article via Infotrieve]
10. Rayssiguier Y, Mbega JD, Durlach V, Gueux E, Durlach J, Giry J, Dalle M, Mazur A, Laurant P, Berthelot A. Magnesium and blood pressure, I: animal studies. Magnes Res. 1995;5:139–146.
11. Morrill GA, Gupta PK, Kostellow AB, Ma GY, Zhang A, Altura BT, Altura BM. Mg2+ modulates membrane lipids in vascular smooth muscle: a link to atherogenesis. FEBS Lett. 1997;408:191–194.[Medline] [Order article via Infotrieve]
12. Resnick LM, Laragh JH, Sealey JE, Alderman MH. Divalent cations in essential hypertension. N Engl J Med. 1983;309:889–891.
13.
Miyagi H, Yasue H, Okumura K, Ogawa H, Goto K, Oshima
S. Effect of magnesium on anginal attack induced by hyperventilation in
patients with variant angina. Circulation. 1989;79:597–602.
14.
Sueta CA, Clarke SW, Dunlap SH, Jensen L, Blauwet MB,
Koch G, Patterson JH, Adams KF. Effect of acute magnesium
administration on the frequency of ventricular
arrhythmia in patients with heart failure.
Circulation. 1994;89:660–666.
15. Lichodziejewska B, Ktos J, Rezler J, Grudzka K, Dtuzniewska M, Budaj A, Ceremuzynski L. Clinical symptoms of mitral valve prolapse are related to hypomagnesemia and attenuated by magnesium supplementation. Am J Cardiol. 1997;79:768–772.[Medline] [Order article via Infotrieve]
16. Fiset C, Kargacin ME, Kondo CS, Lester WM, Duff HJ. Hypomagnesemia: characterization of a model of sudden cardiac death. J Am Coll Cardiol. 1996;27:1771–1776.[Abstract]
17. Anderson TW, LeRiche WH, MacKay JS. Sudden death and ischemic heart disease: correlation with hardness of local water supply. N Engl J Med. 1969;280:805–807.
18. Gottlieb SS, Baruch L, Kukin ML, Bernstein JL, Fisher ML, Packer M. Prognostic importance of the serum magnesium concentration in patients with congestive heart failure. J Am Coll Cardiol. 1990;16:827–831.[Abstract]
19. Bean BL, Varghese PJ. Role of dietary magnesium deficiency in the pressor and arrhythmogenic response to epinephrine in intact dog. Am Heart J. 1994;127:96–102.[Medline] [Order article via Infotrieve]
20.
Akselrod S, Eliash S, Oz O, Cohen RJ.
Hemodynamic regulation in SHR: investigation by
spectral analysis. Am J Physiol. 1987;253:H176–H183.
21.
Brown DR, Brown LV, Patwardhan A, Randall D.
Sympathetic activity and blood pressure are tightly coupled at 0.4Hz in
conscious rats. Am J Physiol. 1994;267:R1378–R1384.
22. Kevy MN, Yang T, Wallick DW. Assessment of beat-by-beat control of heart rate by the autonomic nervous system: molecular biology techniques are necessary, but not sufficient. J Cardiovasc Electrophysiol. 1993;4:183–193.[Medline] [Order article via Infotrieve]
23.
Mortara A, Rovere MTL, Signorini MG, Pantaleo P,
Pinna G, Martinelli L, Ceconi C, Cerutti S, Tavazzi L. Can power
spectral analysis of heart rate variability identify a high
risk subgroup of congestive heart failure patients with excessive
sympathetic activation? Br Heart J. 1994;71:422–430.
24. Murasato Y, Hirakawa H, Harada Y, Nakamura T, Hayashida Y. Effects of systemic hypoxia on R-R interval and blood pressure variabilities in conscious rats. Am J Physiol. 1998;275:H797–H804.
25.
Pagani M, Montano N, Porta A, Malliani A, Abboud FM,
Birkett C, Somers VK. Relationship between spectral components of
cardiovascular variabilities and direct measures of
muscle sympathetic nerve activity in humans. Circulation. 1997;95:1441–1448.
26.
Pagani M, Lombardi F, Guzzetti S, Rimoldi O, Furlan R,
Pizzinelli O, Sandrone G, Malfatto G, Dell'Orto S, Piccaluga E, Turiel
M, Baseelli G, Cerutti S, Malliani A. Power spectral analysis
of heart rate and arterial pressure variabilities as a
marker of sympatho-vagal interaction in man and conscious dog.
Circ Res. 1986;59:178–193.
27.
Persson PB, Stauss H, Chung O, Wittmann U, Unger T.
Spectrum analysis of sympathetic nerve activity and blood
pressure in conscious rats. Am J Physiol. 1992;263:H1348–H1355.
28.
van de Borne P, Montano N, Pagani M, Oren R, Somers VK.
Absence of low-frequency variability of sympathetic nerve activity in
severe heart failure. Circulation. 1997;95:1449–1454.
29. Schwartz PJ, Rovere MTL, Vanoli E. Autonomic nervous system and sudden cardiac death: experimental basis and clinical observation for post–myocardial infarction risk stratification. Circulation. 1992;85(suppl I):I-77–I-91.
30.
Hirakawa H, Nakamura T, Hayashida Y. Effect of carbon
dioxide on autonomic cardiovascular response to
systemic hypoxia in conscious rats. Am J
Physiol. 1997;273:R747–R754.
31. Kent BB, Drane JW, Blumenstein B, Manning JW. A mathematical model to assess changes in the baroreflex. Cardiology. 1972;57:295–310.[Medline] [Order article via Infotrieve]
32.
DiBona GF, Jones SY, Brooks VL. ANG II receptor
blockade and arterial baroreflex regulation of renal nerve
activity in cardiac failure. Am J Physiol. 1995;269:R1189–R1196.
33. Vanhoutte PM. Serotonin and the vascular wall. Int J Cardiol. 1987;14:189–203.[Medline] [Order article via Infotrieve]
34. von Euler US, Lishajko F. Effect of Mg2+ and Ca2+ on noradrenaline release and uptake in adrenergic nerve granules in different media. Acta Physiol Scand. 1973;89:1847–1849.
35.
Anast CS, Mohs JM, Kaplan SL, Burns TW. Evidence for
parathyroid failure in magnesium deficiency. Science. 1972;177:606–608.
36.
Mak IT, Komarov AM, Wagner TL, Stafford RE, Dickens BF,
Weglicki WB. Enhanced NO production during Mg deficiency and
its role in mediating red cell glutathione loss. Am J
Physiol. 1996;271:C385–C390.
37.
Huang BS, Yuan B, Leenen FHH. Blockade of brain
`ouabain' prevents the impairment of baroreflexes in rats after
myocardial infarction. Circulation. 1997;96:1654–1659.
38.
Nishizawa M, Kumagai H, Ichikawa M, Oshima N, Suzuki H,
Saruta T. Improvement in baroreflex function by an oral
angiotensin receptor antagonist in rats with
myocardial infarction. Hypertension. 1997;29:458–463.
39.
Bristow MR, Anderson FL, Port DJ, Sker IL, Hershberger
RE. Differences in ß-adrenergic neuroeffector mechanisms in
ischemic versus idiopathic dilated
cardiomyopathy. Circulation. 1991;84:1024–1039.
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