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Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka 812-82, Japan
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ABSTRACT |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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We
examined the role of central nitric oxide (NO) in the baroreceptor
reflex in conscious rabbits. Intracerebroventricular infusion of 20 µmol of N 
-nitro-L-arginine
methyl ester (L-NAME) to block
central NO resulted in increases in arterial pressure, renal
sympathetic nerve activity (RSNA), and plasma catecholamine levels, and
the pressor response was suppressed by pretreatment with pentolinium (5 mg/kg iv). On the other hand, a subpressor dose of
intracerebroventricular L-NAME
(10 µmol/h) caused significant increases in baroreflex sensitivities
assessed by RSNA and heart rate compared with vehicle infusion
[maximum gain: 
18.2 ± 0.9 vs. 9.6 ± 0.9%/mmHg (P < 0.001) and
14.3 ± 2.3 vs. 5.7 ± 0.4 beats · min
1 · mmHg1
(P < 0.05), respectively].
Conversely, an intracerebroventricular infusion of
Et2N[N(O)NO]Na, an NO
donor (1 µmol/h) significantly attenuated the baroreflex
sensitivities. However, intracerebroventricular infusion of
N -nitro-D-arginine
methyl ester (10 µmol/h), an enantiomer of
L-NAME, failed to alter the
baroreflex sensitivities. These results suggest that
1) the pressor response induced by
inhibition of central NO synthesis is mainly mediated by the enhanced
sympathetic outflow and 2) central
NO attenuates the baroreflex control of RSNA and heart rate in
conscious rabbits.
catecholamines; central nervous system; renal sympathetic nerve activity; sympathetic nervous system
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INTRODUCTION |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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NITRIC OXIDE (NO), which accounts for endothelium-dependent vasodilatation, is synthesized from L-arginine in the presence of its synthetic enzyme NO synthase (NOS) (24). Immunocytochemical studies have revealed that high concentrations of NOS are also present in the specific regions of the brain involved in the regulation of arterial pressure and the baroreceptor reflex (14, 29). Various lines of evidence suggest that NO participates in cardiovascular regulation not only by its direct effect on vascular smooth muscle but also via its action on the central nervous system (9, 12, 25, 28).
NO is now considered to be a neurotransmitter or a neuromodulator in the central nervous system (8, 9). Central inhibition of NO synthesis causes increases in arterial pressure and renal sympathetic nerve activity (RSNA) (27). Conversely, central administration of an NO donor decreases arterial pressure (1). However, the pressor mechanisms induced by central inhibition of NO production, including responses of plasma catecholamine and vasopressin (AVP) levels, have not been fully determined. Moreover, the effects of systemic inhibition of NO synthesis on the baroreceptor reflex are still controversial. Because the baroreceptor reflex and sympathetic outflow are modulated by anesthesia (15, 20), we elected to study conscious animals. Liu et al. (18) revealed that systemic blockade of NO synthesis increases the baroreflex control of RSNA and heart rate (HR); however, they were not able to conclude whether NO acts to modulate baroreflex control in the central nervous system or peripherally. Microinjection studies also have suggested that NO acts at the sites involved in integration of the arterial baroreceptor reflex, such as the nucleus tractus solitarius and the ventrolateral medulla (12, 28). Thus the present study was designed particularly to investigate the role of central NO in baroreflex gains of RSNA and HR in conscious rabbits.
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MATERIALS AND METHODS |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Preparation of animals. The experiments were conducted on male Japanese White rabbits weighing 2.5-3.0 kg. All experiments were carried out according to the institutional guidelines for animal experimentation at Kyushu University. Rabbits were anesthetized with pentobarbital sodium (30 mg/kg iv). Three days before experimentation, bipolar electrodes were implanted on the left renal sympathetic nerve, and a stainless steel cannula was placed in the right lateral cerebral ventricle. RSNA was recorded as described previously (21, 22). Briefly, under aseptic conditions, the left kidney was exposed retroperitoneally, and a branch of the renal nerve was separated from the renal plexus and the surrounding connective tissues with the use of a dissecting microscope. RSNA was recorded by a pair of electrodes made from Teflon-insulated seven-stranded steel wire (Medwire, Mt. Vernon, NY). The area of the nerve and wire interface was embedded in silicone cement (Silgel 604A and B cement, Wacker Chemicals East Asia, Tokyo, Japan).
A 23-gauge stainless steel cannula was implanted into the right lateral cerebral ventricle, 4 mm lateral to the bregma and 6 mm below the cerebral surface. The position of the cannula in the lateral cerebral ventricle was confirmed by the staining of all four ventricles after injection of 0.1 ml of dye at the end of the experiments. The cannula was fixed to the skull with three jeweler's screws and dental cement. A 27-gauge obturator was used to seal the cannula. After surgery, disodium sulbenicillin (200 mg iv) was given to the rabbits to prevent postoperative infections. At least 3 days after the surgical procedures, the following experiments were carried out on conscious rabbits placed in the holding box. On the experimental day, polyethylene catheters (PE-50) were inserted into the central ear artery and marginal ear vein under 1% lidocaine local anesthesia. The arterial catheter was connected to a pressure transducer (model P50, Gould, Oxnard, CA) to measure arterial pressure. HR was monitored using a cardiotachometer (model 1332, NEC San-ei, Tokyo, Japan). All drugs for intracerebroventricular infusion were dissolved in artificial cerebrospinal fluid (aCSF; in mmol/l: 133.3 NaCl, 3.4 KCl, 1.3 CaCl2, 1.2 MgCl2, 0.6 NaH2PO4, 32.0 NaHCO3, and 3.4 glucose).Relationship between dose of intracerebroventricular
N-nitro-L-arginine methyl
ester and cardiovascular responses.
To determine the dose of
N-nitro-L-arginine methyl ester
(L-NAME; Sigma Chemical, St.
Louis, MO) needed to increase arterial pressure, 5, 10, 20, and 40 µmol of L-NAME were injected
intracerebroventricularly (n = 5 for
each). These doses of L-NAME were
dissolved in 80 µl of aCSF. The administration of each dose of
L-NAME was separated by 30 min.
Effect of intracerebroventricular infusion of L-NAME on cardiovascular and neurohormonal responses. After a control period, a blood sample (2.4 ml) was drawn from the arterial catheter to measure plasma catecholamines (epinephrine and norepinephrine), plasma AVP, plasma glucose, plasma osmolality, and hematocrit; then L-NAME (20 µmol) in a volume of 80 µl was injected via the intracerebroventricular cannula (n = 6). Additional blood samples were drawn at 5, 20, and 60 min after intracerebroventricular infusion of L-NAME and were replaced by the same volume of 0.9% saline. Arterial pressure, HR, and RSNA were monitored continuously.
Effect of pentolinium on cardiovascular responses induced by intracerebroventricular infusion of L-NAME. After a control period the rabbits were injected with pentolinium (Sigma Chemical, St. Louis, MO; 5 mg/kg in 0.3 ml/kg iv), a ganglion blocking agent. Five minutes later, L-NAME (20 µmol) was injected intracerebroventricularly (n = 4). Arterial pressure, HR, and RSNA were monitored continuously.
Effect of intravenous infusion of L-NAME on cardiovascular and sympathetic responses. To evaluate the leakage of intracerebroventricularly infused L-NAME into the systemic circulation, the same dose of L-NAME (20 µmol) used in the intracerebroventricular infusion experiment was injected intravenously (n = 4). Arterial pressure, HR, and RSNA were monitored continuously.
Effect of intracerebroventricular infusion of
L-NAME on baroreflex sensitivity.
Three days after the surgical procedure, the effects of
L-NAME on baroreflex control of
RSNA and HR were determined (n = 6). aCSF or L-NAME was infused with
a compact syringe pump (model 100, Muromachi Kikai, Tokyo, Japan) at a
flow rate of 300 µl/h. Fifteen minutes after the beginning of the
intracerebroventricular infusion of aCSF or
L-NAME (10 µmol/h), the
sensitivities of the baroreflex control of RSNA and HR were determined
as follows: progressive infusion of sodium nitroprusside (5-80
µg · kg1 · min1
diluted in 0.9% NaCl) was performed at flow rates of 0.029-0.467 ml/min with a compact infusion pump (model STC-523, Terumo, Tokyo, Japan) for 2 min to induce a 25- to 30-mmHg decrease in mean arterial pressure (MAP). Phenylephrine (2-32
µg · kg1 · min1
diluted in 0.9% NaCl) was infused at flow rates of 0.029-0.933 ml/min for 3 min to induce a 30-mmHg increase in MAP. One-half of the
rabbits were infused first with sodium nitroprusside and then with
phenylephrine; the remaining rabbits received an infusion of
phenylephrine before sodium nitroprusside. At least 30 min elapsed
between the infusion of each vasoactive agent. Before infusions of
sodium nitroprusside and phenylephrine, MAP, HR, and RSNA were
ascertained to be within 10% of their preinfusion levels. The control
values of MAP, HR, and RSNA were taken as their 3-min averages before
each infusion. The values of the mean RSNA before each infusion were
defined as 100%.
Effect of intracerebroventricular infusion of
Et2N[N(O)NO]Na on baroreflex
sensitivity.
Three days after the surgical procedure, the effect of
Et2N[N(O)NO]Na
(NOC-18, Dojindo Institute, Kumamoto, Japan; 1 µmol/h), an NO donor,
on baroreflex control of RSNA and HR was determined (n = 6). Fifteen minutes after the
beginning of the intracerebroventricular infusion of aCSF (300 µl/h)
or NOC-18 (1 µmol · 300 µl1 · h1),
the sensitivities of the baroreflex control of RSNA and HR were
determined as in the L-NAME
experiment.
Effect of intracerebroventricular infusion of
N-nitro-D-arginine
methyl ester on baroreflex sensitivity.
Three days after the surgical procedure, the effect of
N-nitro-D-arginine
methyl ester (D-NAME; Sigma
Chemical), an enantiomer of
L-NAME, on baroreflex control of
RSNA and HR was determined (n = 5).
Fifteen minutes after the beginning of the intracerebroventricular infusion of aCSF (300 µl/h) or
D-NAME (10 µmol · 300 µl1 · h1),
the sensitivities of the baroreflex control of RSNA and HR were
determined as in the L-NAME
experiment.
![RSNA or HR = P<SUB>1</SUB>/ {1 + exp [P<SUB>2</SUB> (MAP − P<SUB>3</SUB> )]} + P<SUB>4</SUB>](/content/vol274/issue4/fulltext/R1142/img001.gif)
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P1 × P2 / 4) calculated
from the parameters of the logistic function curve was considered to be
the sensitivity of the baroreceptor reflex. The slope of the logistic
curve at any given MAP was calculated with the computer from the first
derivative of the equation described above.
Recording procedures of RSNA. RSNA was amplified (model DPA-100E, Dia Medical System, Tokyo, Japan) and filtered (100-3,000 Hz), and the waveforms were integrated after a full-wave rectification using an integrator-amplifier (model 1322, NEC San-ei) with the sample-hold function reset to baseline by an internal timer set at 5 s. Absolute values for integrated RSNA were corrected before the data analysis by subtracting the residual electrical output (noise level) recorded from the integrator induced by an intravenous injection of phenylephrine (32 µg/kg).
Blood collection and analysis.
Blood samples for measurement of plasma catecholamines and plasma AVP
were centrifuged at 4°C. Plasma for catecholamines was stored at
80°C, and other plasma was stored at 20°C until
assay. The plasma catecholamine concentrations were measured by
high-performance liquid chromatography (30), and plasma AVP levels were
measured by RIA (21, 22). The assay sensitivities for AVP and
catecholamines (epinephrine and norepinephrine) were 0.45 pg/ml and
0.01 ng/ml, respectively. Plasma glucose levels were measured by a
Glucose Analyzer 2 (Beckman Instruments, Fullerton, CA). Plasma
osmolality was measured with a freezing-point osmometer (Osmotron-20,
Orion Riken, Tokyo, Japan).
Statistics. Values are means ± SE. To determine the effects of intracerebroventricular and intravenous infusions of L-NAME on cardiovascular and neurohormonal responses, a one-way ANOVA with repeated measurements was performed, followed by Duncan's multiple-range test to determine which means differed from the control means. A paired t-test was used to determine the effects of intracerebroventricular infusion of L-NAME, NOC-18, and D-NAME on baroreflex control. P < 0.05 was considered significant.
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RESULTS |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Relationship between dose of intracerebroventricular L-NAME and cardiovascular responses. Baseline values for MAP and HR before L-NAME intracerebroventricular injections were 83.6 ± 3.4 mmHg and 219.0 ± 7.5 beats/min, respectively. Intracerebroventricular injection of L-NAME elicited dose-related increases in MAP and RSNA and a decrease in HR (Fig. 1). Because 20 µmol of L-NAME caused significant changes in MAP and RSNA, we used this dose of L-NAME in the next experiment.
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Effect of intracerebroventricular L-NAME infusion on cardiovascular and neurohormonal responses. Intracerebroventricular injection of 20 µmol of L-NAME provoked prompt increases in MAP and RSNA, and peak values were obtained after 5 min (Fig. 2). After peak values were obtained, MAP decreased and returned to the baseline levels at 30-60 min. However, HR did not show any significant changes. Table 1 shows the effects of intracerebroventricular infusion of L-NAME on plasma catecholamines and AVP concentrations and other variables. Intracerebroventricular infusion of L-NAME caused significant increases in plasma epinephrine and norepinephrine concentrations at 5 min. Plasma norepinephrine concentration returned to the control value at 20 min; however, plasma epinephrine concentration was still significantly higher at 60 min after intracerebroventricular injection of L-NAME. Plasma AVP levels increased at 5 min but did not reach significance. Plasma osmolality and hematocrit did not show any changes; however, plasma glucose levels increased significantly at 20 and 60 min.
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Effect of pentolinium on cardiovascular responses induced by intracerebroventricular L-NAME infusion. After pentolinium administration, MAP fell from 85.5 ± 1.0 to 64.5 ± 2.4 mmHg and HR increased from 206.3 ± 26.3 to 222.5 ± 27.5 beats/min within 5 min. However, intracerebroventricular L-NAME infusion caused only a small increase in MAP at 5 min (79.0 ± 3.3 mmHg), and RSNA was almost suppressed throughout the entire experimental period.
Effect of intravenous L-NAME infusion on cardiovascular and sympathetic responses. The same dose of L-NAME (20 µmol) used in the intracerebroventricular experiment was injected intravenously. After intravenous injection of L-NAME, arterial pressure, HR, and RSNA remained within 5% of their control values.
Effect of intracerebroventricular infusion of
L-NAME on baroreflex sensitivity.
Figure 3 illustrates representative traces
of arterial pressure, HR, and RSNA in the assessment of baroreceptor
reflex function during intracerebroventricular infusion of
L-NAME in a conscious rabbit.
Intracerebroventricular infusion of
L-NAME (10 µmol/h) did not
cause any changes in MAP, HR, and RSNA, but it significantly enhanced
the baroreflex control of RSNA
(Gmax: 18.2 ± 0.9 vs. 9.6 ± 0.9%/mmHg, P < 0.001; Fig. 4,
A and
B) and HR
(Gmax: 14.3 ± 2.3 vs. 5.7 ± 0.4 beats · min1 · mmHg1,
P < 0.05; Fig.
5, A and
B, Tables
2 and 3).
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Effect of intracerebroventricular infusion of NOC-18 on baroreflex
sensitivity.
Intracerebroventricular infusion of NOC-18 (1 µmol/h) did not change
MAP, HR, and RSNA, although it significantly attenuated the baroreflex
control of RSNA (Gmax: 5.9 ± 0.9 vs. 9.1 ± 1.1%/mmHg, P < 0.01; Fig. 4,
C and
D) and HR
(Gmax: 3.4 ± 0.5 vs.
5.7 ± 0.8 beats · min1 · mmHg1,
P < 0.05; Fig. 5,
C and
D, Tables 2 and 3).
Effect of intracerebroventricular infusion of
D-NAME on baroreflex sensitivity.
Intracerebroventricular infusion of
D-NAME did not change the
baroreflex control of RSNA (Gmax:
8.2 ± 1.5 vs. 8.7 ± 1.3%/mmHg) and HR
(Gmax: 5.7 ± 1.0 vs.
5.6 ± 1.6 beats · min1 · mmHg1;
Fig. 6, Tables 2 and 3).
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DISCUSSION |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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In the present study we have shown the pressor response induced by the blockade of central NO production in conscious rabbits. The use of intracerebroventricular L-NAME infusion to block endogenous NO in the central nervous system caused significant increases in MAP, RSNA, and plasma catecholamine levels; however, intravenous pentolinium, a ganglion blocking agent, suppressed the pressor response. Thus the pressor response induced by intracerebroventricular L-NAME infusion can be attributed primarily to the enhanced sympathetic outflow. Furthermore, the same dose of intravenous L-NAME used in the intracerebroventricular injection did not elicit any cardiovascular or sympathetic responses, suggesting that these responses were not caused by a leakage of intracerebroventricularly infused L-NAME into the systemic circulation. Sakuma et al. (25) and Togashi et al. (27) revealed that systemic and central inhibition of NO synthesis augmented sympathetic outflow, which was blocked by spinal C1-C2 transsection in anesthetized rats. These previous reports support the results of the current study. However, acute systemic NO inhibition increased blood pressure but decreased HR, muscle sympathetic nerve activity, and plasma norepinephrine levels in humans (2, 11). Häbler et al. (10) also reported that intravenous injection of L-NAME increased arterial pressure and decreased postganglionic sympathetic nerve activity in anesthetized rats. A possible explanation for the divergent responses of sympathetic outflow caused by blockade of endogenous NO production is that different pressor mechanisms may be involved in inhibition of central and peripheral NO synthesis. Pressor responses induced by systemic inhibition of NO synthesis may be attributed primarily to the vasoconstriction of peripheral resistance arteries and compensated suppression of sympathetic outflow through the baroreceptor reflex. Central administration of an NOS inhibitor acted at the central nervous system to augment sympathetic outflow, leading to an increase in blood pressure.
Intracerebroventricular infusion of L-NAME induced hyperglycemia in the present study (Table 1). Because hyperglycemia has been shown to be evoked by an increase in plasma epinephrine levels (3), this response of plasma glucose was likely attributable to the increased plasma epinephrine level. On the other hand, the plasma AVP level increased after an intracerebroventricular injection of L-NAME but did not reach a significant level. In the present study, because neither plasma osmolality nor hematocrit changed throughout the entire experimental period and increased plasma levels of epinephrine and norepinephrine would be expected to cause an increase in venous return (5), the changes in the central venous pressure were not considered to stimulate the release of AVP. Moreover, it has been shown that NO also acts at the paraventricular nucleus to regulate blood pressure (13). Thus intracerebroventricular L-NAME infusion might directly stimulate the paraventricular nucleus, leading to the release of AVP into the systemic circulation. Because intravenous pentolinium did not completely abolish the pressor response induced by intracerebroventricular L-NAME infusion, increased circulating AVP might contribute to the remaining pressor response after sympathetic blockade by pentolinium.
To eliminate the peripheral action of NO and to obtain a steady-state level of NOS inhibition or supplementation of NO in the central nervous system, we infused small doses of L-NAME, NOC-18, or D-NAME intracerebroventricularly with a syringe pump. Subpressor dose of an intracerebroventricular infusion of L-NAME augmented the baroreflex control of RSNA and HR. The effects of NO on the baroreceptor reflex have been controversial, probably because of the anesthesia or the elevation of baseline blood pressure caused by blockade of systemic NO production. Kumagai et al. (17) and Liu et al. (18) reported that systemic inhibition of NO enhanced the baroreflex control of RSNA and HR in conscious animals, whereas Jimbo et al. (16) and Du et al. (4) showed that systemic inhibition of NO did not alter the baroreflex sensitivity. Intracerebroventricular infusion of L- and D-arginine was reported to increase blood pressure (23), suggesting that arginine by itself may have some nonspecific excitatory actions in the brain. Thus we decided to use NOC-18 as an NO donor. Intracerebroventricular NOC-18 has not shown this adverse pressor effect (1). Intracerebroventricular infusion of NOC-18 blunted the baroreflex control of RSNA and HR. Furthermore, D-NAME, which is inactive in blocking endogenous NO, did not alter the baroreflex control of RSNA and HR, suggesting that the alteration of baroreflex sensitivity caused by intracerebroventricular infusion of L-NAME was related to blockade of central NO production.
Scrogin et al. (26) reported that the baroreflex control of RSNA is attenuated during chronic inhibition of NO synthesis before the hypertensive stage. These results diverge from our study, probably because of the different effects of chronic and acute blockade of NO on the baroreceptor reflex or the site where the production of NO was blocked in the experiments. NO inhibits mitogenesis and proliferation of vascular smooth muscle cells in culture (7). Chronic, but not acute, inhibition of such processes might affect vascular distensibility and change baroreceptor reflexes.
NO and the NO donor S-nitrosocysteine have been reported to suppress the activity of carotid sinus baroreceptors (19). Thus the carotid sinus may be one of the important sites involved in modulation of the baroreflex by acute systemic inhibition of NO synthesis. However, it is unlikely that the carotid sinus was involved in the modulation of the baroreceptor reflex by intracerebroventricular infusion of L-NAME or NOC-18. Although the current study did not clarify the exact site of NO action in the central nervous system, the nucleus tractus solitarius and the ventrolateral medulla might be candidates for modulation of baroreceptor reflex. However, Harada et al. (12) demonstrated that blockade of NO production in the nucleus tractus solitarius did not alter the baroreflex sensitivity in anesthetized rabbits. Because endogenous and exogenous NO have been shown to regulate blood pressure in the ventrolateral medulla (28), this region might be involved in the modulation of the baroreceptor reflex by central NO. Further studies are necessary to determine the role of NO in the baroreceptor reflex in the ventrolateral medulla. It has not been determined precisely how NO regulates blood pressure and sympathetic outflow in the brain; however, NO may act in an ultrashort loop feedback system, whereby release of glutamate results in activation of NOS and production of NO. This NO, in turn, reaches presynaptic terminals, where it acts to influence the subsequent release of glutamate in response to neuronal activation (8).
Liu et al. (18) showed an enhanced HR, but not RSNA, response to aortic nerve stimulation in chloralose-anesthetized sinoaortic-denervated rabbits with acute systemic inhibition of NO synthesis, and they suggested that the central nervous system plays a more important role in the modulating effect of NO on the baroreflex control of HR than on RSNA (18). In the present study, however, we demonstrated that endogenous and exogenous central NO modulates the baroreflex control of RSNA as well as HR in conscious rabbits. These divergent results may be explained by the use of anesthesia in their experiment. Because anesthesia blunts baroreflex sensitivity and changes the sympathetic outflow (15, 20), different responses of HR and RSNA might be observed.
Perspectives
In summary, inhibition of central NO synthesis exerts a potent pressor response mediated by enhanced sympathoadrenal outflow. Central NO attenuates the baroreflex control of RSNA and HR in conscious rabbits. NO participates in cardiovascular regulation not only by its direct effect on vascular smooth muscle but also via its action on the central nervous system. Central NO probably works as a neurotransmitter or a neuromodulator in the brain and changes sympathetic outflow, although the precise mechanisms have not been determined in the present study. The ventrolateral medulla may be one of the candidates to modulate the baroreceptor reflex. However, further studies are necessary to determine the exact site where NO modulates baroreceptor reflex in the central nervous system.| |
ACKNOWLEDGEMENTS |
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We thank S. Nakamuta, M. Mihara, and K. Zaitsu for expert technical assistance.
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FOOTNOTES |
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This work was supported in part by Ministry of Education, Japan Grant 09770495.
Address for reprint requests: K. Matsumura, Second Dept. of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-82, Japan.
Received 12 September 1997; accepted in final form 2 December 1997.
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REFERENCES |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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1.
Cabrera, C. L.,
S. L. Bealer,
and
D. F. Bohr.
Central depressor action of nitric oxide is deficient in genetic hypertension.
Am. J. Hypertens.
9:
237-241,
1996[Medline].
2.
Castellano, M.,
D. Rizzoni,
M. Beschi,
M. L. Muiesan,
E. Porteri,
G. Bettoni,
M. Salvetti,
A. Cinelli,
R. Zulli,
and
E. Agabiti-Rosei.
Relationship between sympathetic nervous system activity, baroreflex and cardiovascular effects after acute nitric oxide synthesis inhibition in humans.
J. Hypertens.
13:
1153-1161,
1995[Medline].
3.
Cherrington, A. D.,
H. Fuchs,
R. W. Stevenson,
P. E. Williams,
K. G. M. M. Alberti,
and
K. E. Steiner.
Effect of epinephrine on glycogenolysis and gluconeogenesis in conscious overnight-fasted dogs.
Am. J. Physiol.
247 (Endocrinol. Metab. 10):
E137-E144,
1984
4.
Du, Z.-Y.,
G. J. Dusting,
and
O. L. Woodman.
Baroreceptor reflexes and vascular reactivity during inhibition of nitric oxide synthesis in conscious rabbits.
Eur. J. Pharmacol.
214:
21-26,
1992[Medline].
5.
Emerson, T. E., Jr.
Effects of angiotensin, epinephrine, norepinephrine, and vasopressin on venous return.
Am. J. Physiol.
210:
933-942,
1966.
6.
Faris, I. B.,
J. Iannos,
G. G. Jamieson,
and
J. Ludbrook.
Comparison of methods for eliciting the baroreceptor-heart rate reflex in conscious rabbits.
Clin. Exp. Pharmacol. Physiol.
7:
281-291,
1980[Medline].
7.
Garg, U. C.,
and
A. Hassid.
Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells.
J. Clin. Invest.
83:
1774-1777,
1989.
8.
Garthwaite, J.
Glutamate, nitric oxide and cell-cell signaling in the nervous system.
Trends Neurosci.
14:
60-67,
1991[Medline].
9.
Garthwaite, J.,
and
C. L. Boulton.
Nitric oxide signaling in the central nervous system.
Annu. Rev. Physiol.
57:
683-706,
1995[Medline].
10.
Häbler, H.-J.,
G. Wasner,
T. Bartsch,
and
W. Jänig.
Responses of rat postganglionic sympathetic vasoconstrictor neurons following blockade of nitric oxide synthesis in vivo.
Neuroscience
77:
899-909,
1997[Medline].
11.
Hansen, J.,
T. N. Jacobsen,
and
R. G. Victor.
Is nitric oxide involved in the tonic inhibition of central sympathetic outflow in humans?
Hypertension
24:
439-444,
1994
12.
Harada, S.,
S. Tokunaga,
M. Momohara,
H. Masaki,
T. Tagawa,
T. Imaizumi,
and
A. Takeshita.
Inhibition of nitric oxide formation in the nucleus tractus solitarius increases renal sympathetic nerve activity in rabbits.
Circ. Res.
72:
511-516,
1993
13.
Horn, T.,
P. M. Smith,
B. E. McLaughlin,
L. Bauce,
G. S. Marks,
Q. J. Pittman,
and
A. V. Ferguson.
Nitric oxide actions in paraventricular nucleus: cardiovascular and neurochemical implications.
Am. J. Physiol.
266 (Regulatory Integrative Comp. Physiol. 35):
R306-R313,
1994
14.
Iadecola, C.,
P. L. Faris,
B. K. Hartman,
and
X. Xu.
Localization of NADPH diaphorase in neurons of the rostral ventral medulla: possible role of nitric oxide in central autonomic regulation and oxygen chemoreception.
Brain Res.
603:
173-179,
1993[Medline].
15.
Ishikawa, N.,
C. H. Kallman,
and
K. Sagawa.
Rabbit carotid sinus reflex under pentobarbital, urethan, and chloralose anesthesia.
Am. J. Physiol.
246 (Heart Circ. Physiol. 15):
H696-H701,
1984
16.
Jimbo, M.,
H. Suzuki,
M. Ichikawa,
K. Kumagai,
M. Nishizawa,
and
T. Saruta.
Role of nitric oxide in regulation of baroreceptor reflex.
J. Auton. Nerv. Syst.
50:
209-219,
1994[Medline].
17.
Kumagai, H.,
D. B. Averill,
M. C. Khosla,
and
C. M. Ferrario.
Role of nitric oxide and angiotensin II in the regulation of sympathetic nerve activity in spontaneously hypertensive rats.
Hypertension
21:
476-484,
1993
18.
Liu, J.-L.,
H. Murakami,
and
I. H. Zucker.
Effects of NO on baroreflex control of heart rate and renal sympathetic nerve activity in conscious rabbits.
Am. J. Physiol.
270 (Regulatory Integrative Comp. Physiol. 39):
R1361-R1370,
1996
19.
Matsuda, T.,
J. N. Bates,
S. J. Lewis,
F. M. Abboud,
and
M. W. Chapleau.
Modulation of baroreceptor activity by nitric oxide and S-nitrosocysteine.
Circ. Res.
76:
426-433,
1995
20.
Matsukawa, K.,
and
I. Ninomiya.
Anesthetic effects on tonic and reflex renal sympathetic nerve activity in awake cats.
Am. J. Physiol.
256 (Regulatory Integrative Comp. Physiol. 25):
R371-R378,
1989
21.
Matsumura, K.,
I. Abe,
M. Tominaga,
T. Tsuchihashi,
K. Kobayashi,
and
M. Fujishima.
Differential modulation by µ- and 
-opioids on baroreceptor reflex in conscious rabbits.
Hypertension
19:
648-652,
1992
22.
Matsumura, K.,
I. Abe,
T. Tsuchihashi,
M. Tominaga,
K. Kobayashi,
and
M. Fujishima.
Central effect of endothelin on neurohormonal responses in conscious rabbits.
Hypertension
17:
1192-1196,
1991
23.
Nishimura, M.,
H. Takahashi,
A. Nanbu,
M. Sakamoto,
and
M. Yoshimura.
Cardiovascular regulation by L-arginine in the brain of rats: role of the brain renin-angiotensin system and nitric oxide.
Am. J. Hypertens.
10:
389-396,
1997[Medline].
24.
Palmer, R. M. J.,
D. S. Ashton,
and
S. Moncada.
Vascular endothelial cells synthesize nitric oxide from L-arginine.
Nature
333:
664-666,
1988[Medline].
25.
Sakuma, I.,
H. Togashi,
M. Yoshioka,
H. Saito,
M. Yanagida,
M. Tamura,
T. Kobayashi,
H. Yasuda,
S. S. Gross,
and
R. Levi.
NG-methyl-L-arginine, an inhibitor of L-arginine-derived nitric oxide synthesis, stimulates renal sympathetic nerve activity in vivo: a role for nitric oxide in the central regulation of sympathetic tone?
Circ. Res.
70:
607-611,
1992
26.
Scrogin, K. E.,
R. Veelken,
and
F. C. Luft.
Sympathetic baroreceptor responses after chronic NG-nitro-L-arginine methyl ester treatment in conscious rats.
Hypertension
23:
982-986,
1994
27.
Togashi, H.,
I. Sakuma,
M. Yoshioka,
T. Kobayashi,
H. Yasuda,
A. Kitabatake,
H. Saito,
S. S. Gross,
and
R. Levi.
A central nervous system action of nitric oxide in blood pressure regulation.
J. Pharmacol. Exp. Ther.
262:
343-347,
1992
28.
Tseng, C.-J.,
H.-Y. Liu,
H.-C. Lin,
L.-P. Ger,
C.-S. Tung,
and
M.-H. Yen.
Cardiovascular effects of nitric oxide in the brain stem nuclei of rats.
Hypertension
27:
36-42,
1996
29.
Vincent, S. R.,
and
H. Kimura.
Histochemical mapping of nitric oxide synthase in the rat brain.
Neuroscience
46:
755-784,
1992[Medline].
30.
Yoshimura, M.,
T. Komori,
T. Nakanishi,
and
H. Takahashi.
Estimation of sulphoconjugated catecholamine concentrations in plasma by high-performance liquid chromatography.
Ann. Clin. Biochem.
30:
135-141,
1993.
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