Vol. 277, Issue 4, R1057-R1062, October 1999
Role of cholinergic receptors in adrenal catecholamine
secretion in spontaneously hypertensive rats
Takahiro
Nagayama1,
Takayuki
Matsumoto1,
Makoto
Yoshida1,
Mizue
Suzuki-Kusaba1,
Hiroaki
Hisa1,
Tomohiko
Kimura2, and
Susumu
Satoh1
1 Laboratory of Pharamacology,
Graduate School of Pharmaceutical Sciences, Tohoku University,
Sendai 980-8578; and 2 Department
of Dental Pharmacology, The Nippon Dental University School of
Dentistry at Niigata, Niigata 951-8580, Japan
 |
ABSTRACT |
We
investigated the role of nicotinic and muscarinic receptors in
secretion of catecholamines induced by transmural electrical stimulation (ES) from isolated perfused adrenal glands of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. ES
(1-10 Hz) produced frequency-dependent increases in epinephrine (Epi) and norepinephrine (NE) output as measured in
perfusate. The ES-induced increases in NE output, but not Epi output,
were significantly greater in adrenal glands of SHRs than in those of
WKY rats. Hexamethonium (10-100 µM) markedly
inhibited the ES-induced increases in Epi and NE output from adrenal
glands of SHRs and WKY rats. Atropine (0.3-3 µM) inhibited the
ES-induced increases in Epi and NE output from adrenal glands of SHRs,
but not from those of WKY rats. These results suggest that endogenous acetylcholine-induced secretion of adrenal catecholamines is
predominantly mediated by nicotinic receptors in SHRs and WKY rats and
that the contribution of muscarinic receptors may be different between these two strains.
adrenal gland; nicotinic receptors; muscarinic receptors; hexamethonium; atropine
| |
INTRODUCTION |
THERE IS INCREASING evidence suggesting that the
sympathetic nervous system plays an important role in the development
and maintenance of hypertension in spontaneously hypertensive rats (SHRs; Refs. 10, 30). Of particular interest is the importance of the
adrenal medulla in hypertension. It has been reported that the
reduction in plasma catecholamine levels by surgical adrenal demedullation attenuates hypertension development in young SHRs (3, 4)
and that epinephrine (Epi) supplementation induces hypertension in
normotensive rats (23). These findings suggest that the secretion of
adrenal catecholamines may be partially involved in the pathogenesis of
hypertension. A vasoconstrictor hyperresponsiveness to sympathetic
activation has been observed in the isolated organs of SHRs (9, 11,
19), which is thought to be due to enhanced norepinephrine release from
the sympathetic adrenergic nerve terminals (7, 8). However, there has
been no information on the difference between neural control of adrenal catecholamine secretion in hypertensive rats and normotensive rats.
Adrenal medullary chromaffin cells secrete catecholamines into the
bloodstream as a physiological response to stress. This response is
mediated by splanchnic nerve activity. Activation of the splanchnic
nerve causes the release of acetylcholine from its terminal into the
intrasynaptic cleft, and released acetylcholine subsequently stimulates
nicotinic and muscarinic receptors present on the surface of chromaffin
cells. The contribution of muscarinic receptors to catecholamine
secretion in response to splanchnic nerve stimulation is still unclear
and probably varies from one species to another (32). It was reported
that the endogenous acetylcholine-induced catecholamine secretion was
barely affected by atropine and largely reduced by hexamethonium in the
perfused rat adrenal gland (33). However, whether muscarinic receptors contribute functionally to catecholamine secretion from adrenal glands
of SHRs has not been explored.
In the present study, we investigated the effects of hexamethonium and
atropine on the secretion of catecholamines induced by transmural
electrical stimulation (ES) from isolated perfused adrenal glands of
SHRs and normotensive Wistar-Kyoto (WKY) rats to elucidate the
functional role of nicotinic and muscarinic receptors in neural control
of the secretion of adrenal catecholamines in this model of hypertension.
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MATERIALS AND METHODS |
Animals. Male SHRs (246 ± 6 g;
n = 31) and WKY rats (252 ± 7 g; n = 29) of 9 wk of age
were obtained from SLC (Shizuoka, Japan). Rats were maintained in the
animal care facility at an ambient temperature of 23 ± 1°C and
humidity of 55%. Animals were fed a standard diet and had free access
to tap water. Animals were chosen at random for control or test
experiments. All procedures for handling animals were approved by the
Animal Experimentation Committee of Tohoku University Graduate School
of Pharmaceutical Sciences. On the day of the experiment, tail-cuff
recordings were used to be sure that the SHRs were clearly hypertensive.
Surgical preparation. Rats were
anesthetized with pentobarbital sodium (50 mg/kg ip). The left adrenal
gland was exposed by a midline incision of abdomen. The stomach,
intestines, and portions of the liver were pushed over to the right
side and covered by saline-soaked gauze pads to obtain enough working
space for tying blood vessels and for cannulation. A polyethylene
cannula, used for perfusion of the adrenal gland, was inserted into the
adrenal vein through the renal vein after all the branches of the
adrenal vein, the renal artery, and the renal vein were ligated. Then the adrenal gland, along with the tied blood vessels and the cannula, was carefully removed from the animal and a small slit was made into
the adrenal cortex just opposite the entrance of the adrenal vein.
Perfusion of the adrenal gland was started to ensure that no leak was
present, and the perfusate escaped only from the slit of the adrenal
gland. The adrenal gland was placed on a bipolar platinum electrode
used for ES. The adrenal gland together with an electrode was placed in
a water-jacketed chamber, the temperature of which was maintained at
37°C with a thermostatically controlled water circulator (NTT-1200,
Tokyo Rikakikai, Tokyo, Japan).
Perfusion of the adrenal gland. The
adrenal gland was perfused by means of a peristaltic pump (MP-3A, Tokyo
Rikakikai) at a rate of 0.2 ml/min. The perfusion was carried out with
Krebs-Henseleit solution of the following composition (in mM): 118 NaCl, 4.7 KCl, 1.2 MgSO4, 2.6 CaCl2, 1.2 KH2PO4,
24.9 NaHCO3, and 11.1 glucose. Krebs solution was maintained at 37°C by the thermostat bath and bubbled with a mixture of 95% O2
and 5% CO2. Perfusate samples were collected in chilled tubes containing 50 µl of 0.1 M perchloric acid to prevent oxidation of catecholamines. Before starting an experiment, the adrenal gland was initially perfused for 60 min with
Krebs solution.
ES. ES (duration, 1 ms; supramaximal
voltage, 50 V) was applied by a bipolar platinum electrode with an
electronic stimulator (SEN-3301, Nihon Kohden, Tokyo, Japan) and an
isolation unit (SS-302J, Nihon Kohden). Stimulus frequency was raised
stepwise from 1 to 2, 5, and 10 Hz at 5-min intervals, stimulation at
each frequency being applied with 100-pulse trains.
Experimental protocol. The rats were
divided into six groups. In groups
1 (n = 13) and 2 (n = 11), the effects of repeated ES
on increases in catecholamine (Epi and NE) output from adrenal glands
of SHRs and WKY rats were examined, respectively, without drug
treatment. A set of ES was repeated four times at 30-min intervals. In
groups
3 (n = 8) and 4 (n = 10), the effects of hexamethonium
on the ES-induced increases in catecholamine output from adrenal glands
of SHRs and WKY rats were examined, respectively. The first set of ES
trials was regarded as a control. Perfusion with 10, 30, and 100 µM
hexamethonium-Krebs solutions was started 10 min before the start of
the second, third, and fourth set of ES, respectively. In
groups
5 (n = 10) and 6 (n = 8), the effects of atropine (0.3, 1, and 3 µM) on the ES-induced increases in catecholamine output from
adrenal glands of SHRs and WKY rats were examined with the same
protocol as used in groups
3 and
4, respectively. In all groups, the
adrenal gland was weighed after removing the adrenal vein at the end of
the experiment.
Perfusate sampling. Perfusate was
sampled before and during each frequency of ES to determine
catecholamine output. The sampling during the basal state was performed
for 60 s just before ES. In preliminary experiments, it was found that
the catecholamine responses to various frequencies of ES returned to
prestimulation level within ~50 s after stopping the stimulation.
Thus the samplings during ES at 1, 2, 5, and 10 Hz were performed for
150, 100, 70, and 60 s, respectively.
Determination of adrenal catecholamine
output. Catecholamines in perfusate sample were
measured by high-performance liquid chromatography with electrochemical
detection (LC-4C, Bioanalytical Systems, West Lafayette, IN), as
described previously (15). Adrenal Epi and NE output
(ng · min
1 · g1)
were calculated by perfusate catecholamine concentration (ng/ml), perfusion rate (0.2 ml/min), and adrenal gland weight (g). The basal
catecholamine output was determined from samples collected just before
each ES. The ES-induced increases in catecholamine output were
calculated by subtracting basal catecholamine output from that obtained
during the stimulus state.
Analysis of data. The results are
expressed as means ± SE. Student's unpaired
t-test or two-factor ANOVA with
Dunnett's test was used for statistical analysis of data.
P values <0.05 were considered to be
statistically significant.
Drugs. The drugs used were
hexamethonium chloride and atropine sulfate (Sigma Chemical, St. Louis,
MO). Both drugs were dissolved in Krebs-Henseleit solution.
| |
RESULTS |
Increases in catecholamine output in response to
ES. The adrenal gland weights of SHRs
(groups 1,
3, and
5; n = 31) and WKY rats (groups
2, 4,
and 6;
n = 29) were 19.2 ± 0.4 and 22.6 ± 0.7 mg, respectively, and this value in SHRs was significantly
smaller than that in WKY rats (P < 0.01). Basal catecholamine output from adrenal glands of SHRs
(groups 1,
3, and
5; n = 31) and WKY rats (groups
2, 4,
and 6;
n = 29) at 60 min after initial
perfusion were 772 ± 99 and 396 ± 56 ng · min1 · g1
in Epi and 191 ± 27 and 87 ± 12 ng · min1 · g1
in NE, respectively. These values in SHRs were significantly greater
than those in WKY rats (Epi output, P < 0.01; NE output, P < 0.01).
ES (1, 2, 5, and 10 Hz) produced frequency-dependent increases in Epi
and NE output from adrenal glands of SHRs and WKY rats. The increases
in Epi and NE output induced by ES during the four stimulation periods
are shown in Tables 1 and
2, respectively. The increases in
catecholamine output induced by ES did not vary during the time course
of the experiment in adrenal glands of SHRs or WKY rats. The increase
in NE output, but not Epi output, induced by ES (5 and 10 Hz) in SHRs
was significantly greater than that in WKY rats (Tables 1 and 2).
Effects of hexamethonium and atropine on the
ES-induced increases in catecholamine output.
Hexamethonium (10, 30, and 100 µM) inhibited the ES-induced increases
in Epi and NE output from adrenal glands of SHRs and WKY rats (Figs.
1 and 2,
respectively). Atropine (0.3, 1, and 3 µM) significantly attenuated
the ES-induced increases in Epi and NE output from adrenal glands of
SHRs (Fig. 3). The ES-induced increases in
Epi and NE output from adrenal glands of WKY rats were not affected
even by the highest concentration (3 µM) of atropine (Fig.
4). Neither hexamethonium nor atropine affected basal Epi and NE output from adrenal glands of SHRs and WKY
rats (data not shown).
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Fig. 1.
Effects of hexamethonium (Hexa) on epinephrine (Epi;
A) and norepinephrine (NE;
B) output from perfused adrenal
glands of spontaneously hypertensive rats (SHRs) in response to
electrical stimulation (ES). Points and vertical bars represent means ± SE. * P < 0.05, ** P < 0.01 compared
with corresponding control response obtained before hexamethonium
treatment.
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Fig. 2.
Effects of hexamethonium on Epi (A)
and NE (B) output from perfused
adrenal glands of Wistar-Kyoto (WKY) rats in response to ES. Points and
vertical bars represent means ± SE.
* P < 0.05, ** P < 0.01 compared with
corresponding control response obtained before hexamethonium
treatment.
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Fig. 3.
Effects of atropine (Atro) on Epi
(A) and NE
(B) output from perfused adrenal
glands of SHRs in response to ES. Points and vertical bars represent
means ± SE. ** P < 0.01 compared with corresponding control response obtained before atropine
treatment.
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Fig. 4.
Effects of atropine on Epi (A) and
NE (B) output from perfused adrenal
glands of WKY rats in response to ES. Points and vertical bars
represent means ± SE. There were no significant differences
(P > 0.05) in ES-induced increases
in catecholamine output before (control) and during atropine
treatment.
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| |
DISCUSSION |
The aims of this study were to investigate whether SHRs are different
from normotensive WKY rats 1) in the
degree of secretion of catecholamines induced by ES and
2) in the functional contributions of nicotinic and muscarinic receptors to the secretion of
catecholamines. ES produced frequency-dependent increases in Epi and NE
output from adrenal glands of SHRs and WKY rats. Although the
ES-induced Epi secretion was almost to the same degree between the two
strains, the NE response was greater in adrenal glands of SHRs than in those of WKY rats. It has been reported that NE but not Epi content is
higher in adrenal glands of SHRs than in those of WKY rats (6, 20, 21,
26). Thus the facilitated NE secretion in SHRs may be due to higher NE
content in the adrenal gland. Furthermore, NE release induced by ES has
been reported to be greater in the kidney (5) and the perfused
mesenteric arteries (13, 25, 28, 31) of SHRs than in those of WKY rats.
These results and ours have provided evidence suggesting that the
exocytosis of NE from sympathetic nerves in various organs and from the
adrenal gland may be facilitated in the developmental stage of
hypertension. It is thought that SHRs have heightened sympathetic drive
from regions of the brain such as the rostral ventral lateral medulla and hypothalamic paraventricular nucleus. Our results obtained with the
isolated perfused adrenal gland preparation clearly indicate that NE
secretion due to peripheral neuronal excitation was facilitated at the
adrenal glands of SHRs. Therefore it would seem that the augmented
central sympathetic drive combined with augmented stimulated secretion
of NE at the adrenal gland would be a powerful stimulus to support
blood pressure in the SHR.
Hexamethonium markedly inhibited increases in Epi and NE output in
response to ES from adrenal glands of normotensive WKY rats. These
results are consistent with the observations that hexamethonium largely
reduced catecholamine secretion evoked by ES in the perfused rat
adrenal gland (33) and that another nicotinic receptor antagonist,
mecamylamine, inhibited the secretion of catecholamines induced by ES
in the perfused cat adrenal gland (1). In adrenal glands of SHRs,
hexamethonium also inhibited the ES-induced increases in Epi and NE
output. It is reported that neuronally evoked secretion of
catecholamines is mediated by not only acetylcholine but noncholinergic
substances such as opioid peptides and that the contribution of
noncholinergic substances predominates at low neuronal activity
(0.5-1 Hz) in the isolated perfused rat adrenal gland (24).
However, in the present study, secretion of catecholamines from adrenal
glands of SHRs or WKY rats induced by ES at 1 Hz was inhibited by
hexamethonium by >80%. These results suggest that neuronally evoked
secretion of adrenal catecholamines is predominately mediated by
nicotinic receptors in SHRs as well as WKY rats.
Atropine did not affect increases in Epi and NE output in response to
ES from adrenal glands of WKY rats. This result indicates that
muscarinic receptors do not contribute functionally to neuronally evoked secretion of catecholamines in normotensive rats. These findings
agree with the results that atropine has no effect on the splanchnic
nerve stimulation-induced secretion of catecholamines in the rat
adrenal gland (33) and that another muscarinic antagonist, pirenzepine,
does not modify the catecholamine secretion induced by splanchnic nerve
stimulation in the dog adrenal gland (16). On the other hand, atropine
inhibited the ES-induced increases in Epi and NE output from adrenal
glands of SHRs. This is the first study to suggest that neuronally
evoked secretion of catecholamines is mediated by not only nicotinic
but muscarinic receptors in SHRs.
It has been suggested that an augmentation of various receptor
populations may be involved in the development and maintenance of
hypertension in the SHR, such as cholecystokinin receptors in the
nucleus accumbens (18), D1 dopamine receptors in the brain (17),
2-adrenergic receptors in the
locus ceruleus (22), and glomerular endothelin B receptors in the
kidney (14). Therefore, the inhibitory effect of atropine on the
ES-induced secretion of catecholamines from adrenal glands of SHRs
might be explained by the augmentation of muscarinic receptor
populations located on the surface of adrenal medullary chromaffin cells.
In the present study, the basal Epi and NE output were greater in
adrenal glands of SHRs than in those of WKY rats. These results are not
consistent with the observation that there is no significant difference
in basal NE overflow from the perfused mesenteric arteries (13, 28, 31)
and from the isolated synaptosomes of hypothalamus and brain stem (12)
between the two strains. These different results may be due to
differences in the examined organs or tissues. Plasma concentrations of
Epi and NE have been reported to be high in the SHR (2, 27, 29). Our
results suggest that spontaneous Epi and NE secretion from the adrenal gland may be facilitated in the stage of pathogenesis of hypertension, and this facilitation may partially contribute to the elevated plasma
concentrations of Epi and NE in the SHR.
In conclusion, this study demonstrates that the ES-induced increases in
NE output, but not Epi output, were significantly greater in adrenal
glands of SHRs than in those of WKY rats. We also found that
hexamethonium markedly inhibited the ES-induced increases in Epi and NE
output from adrenal glands of SHRs and WKY rats and that atropine
inhibited the ES-induced increases in Epi and NE output from adrenal
glands of SHRs, but not from those of WKY rats. These results suggest
that endogenous acetylcholine-induced secretion of adrenal
catecholamines is predominantly mediated by nicotinic receptors in SHRs
and WKY rats and that the contribution of muscarinic receptors may be
different between these two strains.
Perspectives
In this study, an augmentation of functional contribution of muscarinic
receptors to catecholamine secretion from adrenal glands of SHRs was
observed. However, it is not known whether this result is due to an
augmentation of muscarinic receptor populations or a greater affinity
of atropine for muscarinic receptors. This issue should be clarified in
further studies.
| |
ACKNOWLEDGEMENTS |
This work was supported in part by Research Fellowships of Japan
Society for the Promotion of Science for Young Scientists and by Grant
10877371 for Scientific Research from The Ministry of Education,
Science and Culture, Japan.
| |
FOOTNOTES |
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. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: H. Hisa,
Laboratory of Pharmacology, Graduate School of Pharmaceutical Sciences,
Tohoku Univ., Aobayama, Sendai, 980-8578, Japan (E-mail:
hhisa{at}mail.pharm.tohoku.ac.jp).
Received 25 March 1999; accepted in final form 4 June 1999.
| |
REFERENCES |
1.
Alamo, L.,
A. G. García,
and
R. Borges.
Electrically-evoked catecholamine release from cat adrenals.
Biochem. Pharmacol.
42:
973-978,
1991[Medline].
2.
Bagdy, G.,
K. Szemeredi,
S. J. Listwak,
H. R. Keiser,
and
D. S. Goldstein.
Plasma catecholamine, renin activity, and ACTH responses to the serotonin receptor agonist DOI in juvenile spontaneously hypertensive rats.
Life Sci.
53:
1573-1582,
1993[Medline].
3.
Borkowski, K. R.,
and
P. Quinn.
The effect of bilateral adrenal demedullation on vascular reactivity and blood pressure in spontaneously hypertensive rats.
Br. J. Pharmacol.
80:
429-437,
1983[Medline].
4.
Borkowski, K. R.,
and
P. Quinn.
Adrenalin and the development of spontaneous hypertension in rats.
J. Auton. Pharmacol.
5:
89-100,
1985[Medline].
5.
Collis, M. G.,
C. H. DeMey,
and
P. M. Vanhoutte.
Renal vascular reactivity in the young spontaneously hypertensive rat.
Hypertension
2:
45-52,
1982[Abstract/Free Full Text].
6.
Donohue, S. J.,
R. E. Stitzel,
and
R. J. Head.
Time course of changes in the norepinephrine content of tissues from spontaneously hypertensive and Wistar Kyoto rats.
J. Pharmacol. Exp. Ther.
245:
24-31,
1988[Abstract/Free Full Text].
7.
Ekas, R. D., Jr.,
and
M. F. Lokhandwala.
Sympathetic nerve function and vascular reactivity in spontaneously hypertensive rats.
Am. J. Physiol.
241 (Regulatory Integrative Comp. Physiol. 10):
R379-R384,
1981.
8.
Ekas, R. D., Jr.,
M. L. Steenberg,
M. S. Woods,
and
M. F. Lokhandwala.
Presynaptic - and 
-adrenoceptor stimulation and norepinephrine release in the spontaneously hypertensive rat.
Hypertension
5:
198-204,
1983[Free Full Text].
9.
Folkow, B.,
M. Hallback,
Y. Lundgren,
and
L. Weiss.
Background of increased flow resistance and vascular reactivity in spontaneously hypertensive rats.
Acta Physiol. Scand.
80:
93-106,
1970[Medline].
10.
Gordon, F. J.,
J. R. Haywood,
M. J. Brody,
and
A. K. Johnson.
Effects of lesions of the anteroventral third ventricle (AV3V) on the development of hypertension in spontaneously hypertensive rats.
Hypertension
4:
387-393,
1982[Abstract/Free Full Text].
11.
Haeusler, G.,
and
W. Haefely.
Pre- and postjunctional supersensitivity of the mesenteric artery preparation from normotensive and hypertensive rats.
Naunyn Schmiedebergs Arch. Pharmacol.
266:
18-33,
1970[Medline].
12.
Hano, T.,
Y. Jeng,
and
J. Rho.
Norepinephrine release and reuptake by hypothalamic synaptosomes of spontaneously hypertensive rats.
Hypertension
13:
250-255,
1989[Abstract/Free Full Text].
13.
Hano, T.,
and
J. Rho.
Norepinephrine overflow in perfused mesenteric arteries of spontaneously hypertensive rats.
Hypertension
14:
44-53,
1989[Abstract/Free Full Text].
14.
Hocher, B.,
P. Rohmeiss,
R. Zart,
F. Diekmann,
V. Vogt,
D. Metz,
M. Fakhury,
N. Gretz,
C. Bauer,
K. Koppenhagen,
H. H. Neumayer,
and
A. Distler.
Function and expression of endothelin receptor subtypes in the kidneys of spontaneously hypertensive rats.
Cardiovasc. Res.
31:
499-510,
1996[Medline].
15.
Kimura, T.,
M. Katoh,
and
S. Satoh.
Inhibition by opioid agonists and enhancement by antagonists of the release of catecholamines from the dog adrenal gland in response to splanchnic nerve stimulation: evidence for the functional role of opioid receptors.
J. Pharmacol. Exp. Ther.
244:
1098-1102,
1988[Abstract/Free Full Text].
16.
Kimura, T.,
T. Shimamura,
and
S. Satoh.
Effects of pirenzepine and hexamethonium on adrenal catecholamine release in response to endogenous and exogenous acetylcholine in anesthetized dogs.
J. Cardiovasc. Pharmacol.
20:
870-874,
1992[Medline].
17.
Kirouac, G. J.,
and
P. K. Ganguly.
Up-regulation of dopamine receptors in the brain of the spontaneously hypertensive rat: an autoradiographic analysis.
Neuroscience
52:
135-141,
1993[Medline].
18.
Kirouac, G. J.,
and
P. K. Ganguly.
Up-regulation of cholecystokinin receptors in the nucleus accumbens of the young prehypertensive spontaneously hypertensive rat.
Neurosci. Lett.
191:
197-199,
1995[Medline].
19.
Kubo, T.
Cardiovascular reactivity in renal and spontaneously hypertensive rats.
Arch. Int. Pharmacodyn. Ther.
234:
49-57,
1978[Medline].
20.
Kumai, T.,
M. Tanaka,
M. Watanabe,
and
S. Kobayashi.
Elevated tyrosine hydroxylase mRNA levels in the adrenal medulla of spontaneously hypertensive rats.
Jpn. J. Pharmacol.
65:
367-369,
1994[Medline].
21.
Kumai, T.,
M. Tanaka,
M. Watanabe,
H. Nakura,
and
S. Kobayashi.
Influence of androgen on tyrosine hydroxylase mRNA in the adrenal medulla of spontaneously hypertensive rats.
Jpn. J. Pharmacol.
65:
367-369,
1994.
22.
Luque, J. M.,
A. Guillamon,
and
B. H. Hwang.
Quantitative autoradiographic study on tyrosine hydroxylase mRNA with in situ hybridization and alpha 2 adrenergic receptor binding in the locus coeruleus of the spontaneously hypertensive rat.
Neurosci. Lett.
131:
163-166,
1991[Medline].
23.
Majewski, H.,
L. H. Tung,
and
M. J. Rand.
Adrenaline induced hypertension in rats.
J. Cardiovasc. Pharmacol.
3:
179-185,
1981[Medline].
24.
Malhotra, R. K.,
and
A. R. Wakade.
Non-cholinergic component of rat splanchnic nerves predominates at low neuronal activity and is eliminated by naloxone.
J. Physiol. (Lond.)
383:
639-652,
1987[Abstract/Free Full Text].
25.
Masuyama, Y.,
K. Tsuda,
Y. Kusuyama,
T. Hano,
M. Kuchii,
and
I. Nishio.
Neurotransmitter release, vascular responsiveness and their calcium-mediated regulation in perfused mesenteric preparation of spontaneously hypertensive rats and DOCA-salt hypertension.
J. Hypertens.
2, Suppl, Suppl. 3:
99-102,
1984.
26.
Ozaki, M.,
Y. Suzuki,
Y. Yamori,
and
K. Okamoto.
Adrenal catecholamine content in the spontaneously hypertensive rats.
Jpn. Circ. J.
32:
1367-1372,
1968[Medline].
27.
Pak, C. H.
Plasma adrenaline and noradrenaline concentrations of the spontaneously hypertensive rat.
Jpn. Heart J.
22:
987-995,
1981[Medline].
28.
Shimosawa, T.,
K. Ando,
and
T. Fujita.
Effect of insulin on norepinephrine overflow at peripheral sympathetic nerve endings in young spontaneously hypertensive rats.
Am. J. Hypertens.
9:
1119-1125,
1996[Medline].
29.
Szemeredi, K.,
G. Bagdy,
R. Stull,
I. J. Kopin,
and
D. S. Goldstein.
Sympathoadrenomedullary hyper-responsiveness to yohimbine in juvenile spontaneously hypertensive rats.
Life Sci.
43:
1063-1068,
1988[Medline].
30.
Trippodo, N. C.,
and
E. D. Frohlich.
Similarities of genetic (spontaneous) hypertension. Man and rat.
Circ. Res.
48:
309-319,
1981[Free Full Text].
31.
Tsuda, K.,
and
Y. Masuyama.
Effects of substance P on norepinephrine release from vascular adrenergic neurons in spontaneously hypertensive rats.
Am. J. Hypertens.
4:
327-332,
1991[Medline].
32.
Unger, A.,
and
J. H. Phillips.
Regulation of adrenal medulla.
Physiol. Rev.
63:
787-843,
1983[Free Full Text].
33.
Wakade, A. R.,
and
T. D. Wakade.
Contribution of nicotinic and muscarinic receptors in the secretion of catecholamines evoked by endogenous and exogenous acetylcholine.
Neuroscience
10:
973-978,
1983[Medline].
Am J Physiol Regul Integr Compar Physiol 277(4):R1057-R1062
0002-9513/99 $5.00
Copyright © 1999 the American Physiological Society
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ABSTRACT
INTRODUCTION
