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The Cardiovascular Center and Departments of 1 Neurology and 2 Pharmacology, The University of Iowa College of Medicine and Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242
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ABSTRACT |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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This study examined peripheral mechanisms responsible for changes in mean arterial blood pressure, heart rate, and renal, mesenteric, and hindquarter vascular resistances produced by microinjections of L-glutamate (L-Glu) into the nucleus tractus solitarii (NTS) of conscious rats. Microinjection of L-Glu produced an initial pressor response, bradycardia, and vasoconstriction in each vascular bed. Subsequent hindquarter vasodilation was observed. After prazosin was administered, L-Glu produced initial hypotension that was probably due to reduced cardiac output. This hypotension was followed by hindquarter vasodilation. Inhibition of nitric oxide synthesis did not affect the initial hypotension or bradycardia in rats treated with prazosin, but the first microinjection of L-Glu after administration of prazosin and NG-nitro-L-arginine methyl ester (L-NAME) produced significantly greater hindquarter vasodilation than after administration of prazosin alone. Second and third microinjections of L-Glu produced significantly smaller hindquarter vasodilation. We conclude that 1) hemodynamic effects produced by microinjection of L-Glu into the NTS of conscious rats involves activation of the sympathetic nervous system and 2) release of preformed nitrosyl factors may mediate vasodilation in the hindquarter vascular bed.
autonomic control; hemodynamics; nitric oxide; excitatory amino acids
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INTRODUCTION |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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MICROINJECTION OF the excitatory amino acid
L-glutamate
(L-Glu) into the nucleus tractus
solitarii (NTS) of conscious rats produces a pressor response and
bradycardia (4, 5, 18, 20). The pressor response is virtually abolished
by systemic administration of the
1-adrenoceptor antagonist
prazosin, whereas the bradycardia is unaffected (4). The
bradycardia is abolished by the subsequent systemic administration of
the muscarinic receptor antagonist methylatropine (4). These findings
suggest that L-Glu mediates its
pressor response via activation of sympathetic vasoconstrictor drive to
the peripheral vasculature, whereas it mediates the bradycardia by
activating the cardiac vagus. In contrast to the pressor responses seen
in conscious rats, microinjections of
L-Glu into the NTS of
anesthetized rats produce dose-related decreases in mean arterial
pressure (MAP) and heart rate (HR) (27, 33). The initial decrease in
MAP is not associated with changes in mesenteric or renal vascular
resistances, although dilation gradually develops in these beds (33).
The sequence of changes in hindquarter vascular resistance differs. In
the hindquarter bed, vasodilation occurs immediately after
microinjection of L-Glu, whereas
vasoconstriction develops during the later stage of the depressor
response (33). Because these effects of
L-Glu are virtually abolished by
ganglion blockade (33), they appear to result from changes in autonomic
nerve activity.
The activation and/or withdrawal of sympathetic vasoconstrictor drive may be fully responsible for the hemodynamic effects produced by microinjections of L-Glu into the NTS. However, we have provided evidence that postganglionic lumbar sympathetic nerves innervating the hindquarter vasculature contain nitric oxide (NO) synthase (6, 7) and that the direct and reflex-mediated activation of the lumbar chain produces hindquarter vasodilation via release of newly synthesized and preformed pools of nitrosyl factors (6-9, 25). This raises the possibility that microinjections of L-Glu into the NTS may reduce vascular resistance in the hindquarter bed, in part, by an active sympathetic neurogenic vasodilator process utilizing nitrosyl factors.
At present, there is no information about the effects on vascular resistances when L-Glu is injected into the NTS of conscious rats. Such information would contribute to a better understanding of mechanisms through which glutamatergic systems in the NTS regulate arterial pressure. Therefore, the aims of the present study were to 1) characterize hemodynamic effects produced by microinjection of L-Glu (1 nmol) into the NTS of conscious rats and 2) evaluate the contribution of sympathetic vasoconstrictor and vasodilator processes and of vascular nitrosyl factors in these hemodynamic effects.
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MATERIALS AND METHODS |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Animals. All experiments were performed in conscious, freely moving male Sprague-Dawley rats (n = 23) weighing between 300 and 400 g. The animals were housed individually in Perspex cages in a room with a 12:12-h light-dark cycle. Food and water were freely available except during the experiments.
Surgical procedures. Seven days before the experiments were performed, the rats were anesthetized by administration of halothane (2%) mixed with oxygen (100%). The rats were placed in a stereotaxic frame (model 1940, David Kopf Instruments), and guide cannulas were implanted into the brain using the stereotaxic coordinates of Paxinos and Watson (24), as described previously (4). Briefly, a 15-mm-long stainless steel cannula (22 gauge) was introduced through a cranial window made caudal to lambda. The cannula was positioned 14 mm caudal to bregma, 0.5 mm lateral to the midline, and 7.9 mm below the skull surface at the level of bregma. The tip of the guide cannula was placed in the cerebellum 1.0 mm above the dorsal surface of the brain stem. The guide cannula was fixed with methacrylate to both the skull and the screws inserted in the skull. An occluder closed the cannula until the time of experiments. The needle (33 gauge) used for microinjections into the NTS was 1.5 mm longer than the guide cannula and was connected by PE-10 tubing to a 1-µl syringe (Hamilton, Reno, NV).
Two days before the experiments were performed, the rats were anesthetized by an intraperitoneal injection of a mixture of ketamine (120 mg/kg) and acepromazine maleate (12 mg/kg). Femoral arterial and venous catheters (PE-50) were implanted for measurement of pulsatile arterial blood pressure, MAP, and HR and for administration of drugs, respectively. Immediately after catheterization, a midline laparotomy was performed, and miniature pulsed Doppler flow probes were placed around the lower abdominal aorta, superior mesenteric artery, and left renal artery for measurement of hindquarter, mesenteric, and renal blood flow, respectively. The probes were sutured in place, the leads and catheters were tunneled subcutaneously and exteriorized between the scapulae, and the wounds were closed. To protect the probe wires and polyethylene tubing while allowing animals unrestricted movement during recovery and experimental testing, the free ends of the catheters and Doppler leads were led through a stainless steel skin button connected to a spring-swivel assembly that was mounted to a ring stand clamp and suspended above the cage. The skin button was attached to the skin incision in the scapular region using stainless steel sutures. Details of the Doppler technique, including construction of the probes, reliability of the method for estimation of flow velocity, and quantitative determination of percentage changes in hindquarter, mesenteric, and renal resistances, have been described previously (6, 12, 16).Protocol.
After a 2-day period of recovery, the arterial catheters were connected
to a Beckman Dynograph coupled pressure transducer (Cobe Lab) and the
flow probe leads were connected to a Doppler flowmeter (Dept. of
Bioengineering, University of Iowa, Iowa City, IA) for recording MAP,
HR, and blood flows. In the first study, a group of rats
(n = 7) received microinjections of
L-Glu into the NTS (1 nmol in
100 nl). This dose of L-Glu is
the approximate half-maximal effective dose with respect to changes in
MAP and HR in conscious rats (4). Microinjections of
L-Glu were given twice before
and after systemic administration of the
1-adrenoceptor antagonist
prazosin (100 µg/kg iv) and three times after the subsequent systemic
administration of the NO synthesis inhibitor
NG-nitro-L-arginine methyl
ester (L-NAME; (25 µmol/kg iv). The microinjections of
L-Glu were given 5-10 min
apart. Baseline hemodynamic values were allowed to stabilize for at
least 10 min after the injection of either prazosin or
L-NAME but before the first
microinjection of L-Glu was
given. In the second study, the hemodynamic effects produced by the
systemic injection of the NO donor sodium nitroprusside (5 µg/kg iv)
or the S-nitrosothiol,
S-nitrosocysteine (100 nmol/kg iv) (23), were examined in a group of rats
(n = 8) before and after
administration of prazosin (100 µg/kg iv) and again after subsequent
administration of L-NAME (25 µmol/kg iv). In the third study, the hemodynamic effects produced by
four successive systemic injections of sodium nitroprusside (5 µg/kg
iv) or S-nitrosocysteine (100 nmol/kg
iv) were examined in rats (n = 8)
pretreated with the combination of prazosin (100 µg/kg iv) and
L-NAME (25 µmol/kg iv).
Histology. After the experiments were performed, methylene blue (100 nl of a 2% solution) was microinjected at the same site in the NTS for histological analysis. The animals were killed with an overdose of pentobarbital sodium (100 mg/kg iv) and perfused through the heart with saline followed by 10% buffered Formalin. The brains were stored in buffered Formalin for 2 days, and serial coronal (50 µm) sections were cut and stained by the Nissl method using Giemsa dye (5, 11). Only rats whose microinjection sites were located in the NTS at the level of the calamus scriptorius were used for data analysis. Those animals in which microinjections lay outside the NTS did not manifest hemodynamic effects.
Statistics. All data were expressed as means ± SE and were analyzed by repeated-measures analysis of variance (32) followed by Student's modified t-test with Bonferroni correction for multiple comparisons between means (31).
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RESULTS |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Hemodynamic effects of prazosin and
L-NAME.
The hemodynamic effects produced by systemic injection of the
1-adrenoceptor antagonist
prazosin (100 µg/kg iv) and subsequent injection of the NO synthesis
inhibitor L-NAME (25 µmol/kg
iv) into conscious freely moving rats
(n = 7) are summarized in Table 1. Prazosin produced a significant,
sustained reduction in MAP and hindquarter resistance but did not
produce sustained decreases in either renal or mesenteric resistances.
The rats also displayed sustained tachycardia. The subsequent injection
of L-NAME produced marked and
sustained increases in MAP and vascular resistances accompanied by
bradycardia.
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Hemodynamic effects produced by microinjection of L-Glu into the NTS. A typical example of effects elicited by microinjections of L-Glu (1 nmol) into the NTS of a conscious rat before and after the injection of prazosin (100 µg/kg iv) and the subsequent administration of L-NAME (25 µmol/kg iv) are shown in Fig. 1. L-Glu produced a transient pressor response, bradycardia, and decreases in mesenteric, renal, and hindquarter blood flow. The initial decrease in hindquarter blood flow was followed by a pronounced increase in flow. After the administration of prazosin, the microinjection of L-Glu produced an initial reduction in MAP, HR, and blood flows. Although the depressor effect and reduction in renal blood flow were sustained for >1 min, HR and mesenteric blood flow returned to baseline more rapidly. In contrast, there was a pronounced increase in hindquarter blood flow. Ten minutes after administration of L-NAME, the first microinjection of L-Glu still produced a reduction in MAP and minor changes in mesenteric and renal blood flows, but it then caused a pronounced increase in hindquarter blood flow. Each subsequent injection of L-Glu produced progressively smaller reductions in MAP and increases in hindquarter blood flow, whereas the responses of the other hemodynamic variables did not appreciably change.
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Summary of initial hemodynamic effects produced by
L-Glu (phase I).
The initial hemodynamic effects produced by the microinjections of
L-Glu (1 nmol) into the NTS of
conscious rats before and after the systemic administration of prazosin
(100 µg/kg iv) and then
L-NAME (25 µmol/kg iv) are
shown in Fig. 2. Microinjection of
L-Glu produced an increase in
MAP (+26 ± 5%, P < 0.05) that was accompanied by bradycardia (
38 ± 6%,
P < 0.05) and marked increases in
hindquarter resistance (+307 ± 52%,
P < 0.05), renal resistance (+125 ± 22%, P < 0.05), and
mesenteric resistance (+123 ± 21%,
P < 0.05). The vasoconstriction in
the hindquarter bed was significantly greater than that in the renal
and mesenteric beds (P < 0.05 for
both comparisons). A second microinjection of
L-Glu produced similar responses
(see Fig. 2). After the injection of prazosin, microinjection of
L-Glu into the NTS produced
significant (P < 0.05) decreases in
MAP (21 ± 5%) and HR (51 ± 7%) and a significantly attenuated hindquarter vasoconstriction (94 ± 16%, P < 0.05 compared with preprazosin
values). Prazosin eliminated the effects of
L-Glu on renal vascular
resistance (2 ± 4%, P > 0.05 compared with basal resistance) and mesenteric vascular resistance
(17 ± 8%, P > 0.05 compared with basal resistance). A second microinjection of
L-Glu produced similar responses
in these prazosin-treated rats (see Fig. 2). After subsequent systemic administration of L-NAME,
microinjections of L-Glu into
the NTS produced hemodynamic responses that were not different from
those observed before administration of the NO synthesis inhibitor. Each microinjection of L-Glu
produced virtually identical decreases in HR before and after the
administration of prazosin and after the subsequent administration of
L-NAME (see Fig. 2).
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Summary of late-phase hindquarter vasodilation (phase II).
The initial pressor and vasoconstrictor effects produced by
microinjection of L-Glu into the
NTS were followed by a sustained increase in hindquarter blood
flow. The hemodynamic values during the hindquarter
vasodilator phase before and after the administration of prazosin and
then L-NAME are shown in Fig.
3. This phase consisted of a reduction in
hindquarter resistance but no change in other hemodynamic variables.
Before prazosin was administered, the two injections of
L-Glu into the NTS produced
significant (P < 0.05) and
equivalent reductions in hindquarter resistance of 29 ± 5 and 24 ± 4%, respectively. The two microinjections of
L-Glu given after administration
of prazosin produced decreases in hindquarter resistance of 27 ± 4 and 24 ± 4%, respectively. These vasodilator responses were equivalent to those observed before the administration of prazosin (P > 0.05 for both
comparisons). There were no changes in any of the other hemodynamic
variables (P > 0.05 for all
comparisons). After the systemic administration of
L-NAME, the first microinjection of L-Glu into the NTS produced a
small but significant decrease in MAP (10 ± 2%) that was
accompanied by a pronounced decrease in hindquarter resistance
(43 ± 4%). This vasodilator response was significantly
(P < 0.05) greater than that
observed before administration of the NO synthesis inhibitor. The
microinjection of L-Glu also
significantly reduced renal resistance (19 ± 4%, P < 0.05). The second and third
microinjections of L-Glu
produced progressively smaller decreases in MAP (6 ± 2 and
1 ± 1%, respectively) and hindquarter resistance (25 ± 4 and 9 ± 4%, respectively) but similar decreases in
renal resistance (12 ± 2 and 15 ± 3%, respectively).
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Effects of systemically injected S-nitrosocysteine and sodium nitroprusside. To determine whether diminished hindquarter vasodilation after L-NAME might have resulted from tachyphylaxis to the effects of NO, we studied effects of NO donors systemically administered after prazosin and L-NAME. The decreases in MAP and hindquarter resistance produced by the systemic injection of S-nitrosocysteine (100 nmol/kg iv) or sodium nitroprusside (5 µg/kg iv) to conscious, freely moving rats (n = 8) before and after injection of prazosin (100 µg/kg iv) and then L-NAME (25 µmol/kg iv) are summarized in Table 2. Before prazosin was administered, S-nitrosocysteine and sodium nitroprusside produced significant (P < 0.05) decreases in MAP and hindquarter resistance. The hypotensive and vasodilator effects of S-nitrosocysteine and sodium nitroprusside were augmented after administration of prazosin. The hypotensive and vasodilator effects of S-nitrosocysteine were further augmented after subsequent administration of L-NAME. The effects of prazosin and L-NAME on baseline hemodynamic values in this protocol were similar to those in the L-Glu experiments (see Table 1).
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Microinjections sites within the NTS. A diagrammatic representation of microinjection sites within the brain of the seven rats used in these studies is shown in Fig. 4. These sites were located within the intermediate NTS. There were no hemodynamic responses when microinjection sites were located outside the NTS (data not shown). The success rate in these experiments was 42%.
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DISCUSSION |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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The present study confirms that microinjections of
L-Glu into the NTS of conscious
rats produce a pressor response and bradycardia (4, 5, 18, 20) and that
the pressor response is virtually eliminated by pretreatment with the
1-adrenoceptor antagonist prazosin (4). This study demonstrates that the pressor response is
associated with marked vasoconstriction of hindquarter arteries and
lesser, but still pronounced, increases in vascular resistances in the
renal and mesenteric arterial beds. The exaggerated vasoconstriction in
the hindquarter in comparison with the other vascular beds may be due
to greater activation of sympathetic vasoconstrictor input. However,
the exaggerated vasoconstriction in the hindquarter bed would also be
consistent with the concomitant withdrawal of sympathetic vasodilator
input (6, 8). Microinjection of L-Glu into the NTS produced a
significant decrease in MAP and HR in the rats treated with prazosin,
but the responses were associated with only minor changes in vascular
resistances. These initial decreases in MAP and HR in prazosin-treated
rats were blocked by intravenous administration of the muscarinic
receptor antagonist methylatropine (4), which suggests that the
hypotension was due to a vagally mediated reduction in cardiac output.
The untreated rats displayed a pronounced decrease in hindquarter
resistance once the initial pressor and vasoconstrictor effects
produced by the microinjection of
L-Glu had subsided. It is
unlikely that the decrease in vascular resistance was due to withdrawal
of sympathetic drive and resultant loss of
1-adrenoceptor-mediated vasoconstriction, because this hindquarter vasodilation was unaffected by prazosin. After both prazosin and
L-NAME were administered, the
first microinjection of L-Glu
produced exaggerated hindquarter vasodilation. Such persistent
neurogenic hindquarter vasodilatation occurs with the first stimulus
regardless of the timing of the stimulus after blockade (9) even though
breakdown of NO can be expected within seconds of its synthesis (21).
Therefore, hindquarter vasodilation in response to
L-Glu is not simply due to an
increase in NO synthase activity and subsequent release of newly
synthesized NO (14). However, the second and third microinjections of
L-Glu produced progressively and
substantially smaller responses, suggesting depletion of vasodilating
factors after blockade of NO synthesis. We conjecture that the
vasodilator may be a nitrosyl factor that is released from sympathetic
nerves and is more stable than NO itself. We have demonstrated that
postganglionic lumbar sympathetic nerves innervating the hindquarter
vasculature contain NO synthase (7) and stain for NADPH diaphorase (6), a marker for neuronal NO synthase (13). In addition, we have provided
evidence that direct and reflex-mediated activation of postganglionic
lumbar sympathetic nerves produces hindquarter vasodilation that may
involve release of newly synthesized and preformed pools of nitrosyl
factors from these nerves (6-9, 25). Taken together, these
findings raise the possibility that the hindquarter vasodilation
produced by the microinjection of
L-Glu into the NTS of conscious
rats may be mediated by the release of preformed pools of nitrosyl
factors from the NO synthase-positive lumbar sympathetic nerves
innervating this bed. The progressive diminution of the hindquarter
vasodilator responses in
L-NAME-treated rats would be
consistent with release and gradual depletion of these preformed pools
of nitrosyl factors that cannot be regenerated in the absence of NO
synthesis. In a previous study (9), we found that the first episode of
air-jet stress produced an equivalent and pronounced hindquarter
vasodilation whether it was given 10 or 30 min after the administration
of L-NAME. Therefore, it is unlikely that the progressive diminution of the hindquarter
vasodilation observed in the present study is due to the increasingly
greater inhibition of NO synthesis in the lumbar sympathetic nerve
terminals or vascular endothelium between the time of the first and
third microinjections of L-Glu
(given 10 and 30 min after
L-NAME).
There also is considerable evidence that preformed pools of nitrosyl factors exist in vascular smooth muscle (3, 15, 19, 30). Ignarro (14) has postulated that such preformed pools of nitrosyl factors exist within vascular endothelial cells as well. Although the precise identity of these nitrosyl factors has not been established, possible candidates include S-nitrosothiols such as the putative endothelium-derived relaxing factor S-nitrosocysteine (23), dinitrosyl-iron(II) complexes (29) or iron nitrosyls (26). Determination of whether pools of these nitrosyl factors actually exist in the NO synthase-positive sympathetic terminals must await the development of immunohistochemical or histochemical methods for visualizing these nitrosyl factors.
Although the above findings are consistent with the release of nitrosyl
factors from preformed pools in lumbar sympathetic nerve terminals,
there are several other possible explanations for these findings. For
example, decreases in hindquarter resistance could be due to activation
of a cholinergic vasodilator system that causes release of
endothelium-derived nitrosyl factors. We doubt that cholinergic
mechanisms are responsible in that hindquarter vasodilation produced by
direct activation of the lumbar sympathetic chain is unaffected by the
muscarinic receptor antagonist methylatropine (O. S. Possas and S. J. Lewis, unpublished observations). In those studies the
decrease in hindquarter vascular resistance produced by electrical
stimulation of the lumbar chain (3 V, 20 Hz for 10 s) in
pentobarbital-anesthetized rats (n = 5) before and after administration of methylatropine (1 mg/kg iv) was
48 ± 6 and 43 ± 7%
(P > 0.05), respectively.
Vasodilation in response to
L-Glu could also result from
activation of 
-adrenoceptors (1). However, our own studies
demonstrate that the vasodilator effects of the -adrenoceptor
agonists isoproterenol and epinephrine (1) are not diminished by
L-NAME (6, 28) and are,
therefore, unlikely to be mediated by release of nitrosyl factors.
It could also be possible that peptides derived from nerve terminals or vascular endothelium (see Ref. 2) could be involved in the hindquarter vasodilation seen in this study. However, studies from our laboratory do not support this mechanism. We have found that hindquarter vasodilation produced by systemic injection of several peptides, including pituitary adenylate cyclase-activating polypeptide (28), vasoactive intestinal polypeptide, and calcitonin gene-related polypeptide (E. J. Whalen and S. J. Lewis, unpublished observations), are unaffected by the administration of L-NAME and are therefore not likely to be related to release of nitrosyl factors.
Finally, it is possible that the hindquarter vasodilation is mediated by a neurogenically derived agent (peptide or other). Because the actions of this putative agent progressively diminish on repeated administration in L-NAME-treated rats, the agent might mobilize nitrosyl factors from preformed pools in vascular endothelium or lumbar sympathetic nerve terminals. Alternatively, the vasodilator actions of this agent could be independent of nitrosyl factors that nonetheless could, through their own action on vascular smooth muscle, modulate responses to the unknown agent. There is currently no evidence to support this possibility.
It is possible that the loss of hindquarter vasodilation may be due to the diminution of the vasorelaxant potencies of NO or nitrosyl factors. However, the present study demonstrates that four successive systemic injections of the NO donor sodium nitroprusside or the S-nitrosothiol, S-nitrosocysteine, produced similar responses in L-NAME-treated rats. The progressive loss of hindquarter vasodilation in response to repeated microinjections of L-Glu into the NTS may simply be due to the development of tachyphylaxis to glutamate in the NTS or the actions of L-NAME in this nucleus, because it has been demonstrated that L-Glu evokes the release of an endothelium-derived relaxing factor-like substance in the NTS (10). However, it may be unlikely that tachyphylaxis to glutamate is responsible for our observations, because multiple microinjections of L-Glu into the NTS of conscious rats produce similar pressor and bradycardic responses (20). Moreover, in the present study, each of the seven microinjections of L-Glu given in the NTS (including those given after the administration of L-NAME) produced virtually identical decreases in HR. In addition, the microinjection of L-Glu into the NTS of the rats treated with prazosin and L-NAME produced a significant vasodilation in the renal bed. Although we have not determined the mechanisms responsible for this vasodilation, each of the microinjections of L-Glu produced virtually identical falls in renal resistance. Consequently, it appears that tachyphylaxis does not readily develop to the hemodynamic responses produced by the multiple microinjection of L-Glu into the NTS of conscious L-NAME-treated rats.
Ma et al. (17) reported that the systemic injection of
L-NAME (10 mg/kg iv) directly
influenced the activity of neurons within the NTS. Therefore, it is
possible that the use-dependent loss of hindquarter vasodilation in
rats treated with L-NAME may be
due to the actions of the NO synthase inhibitor in the NTS. If this
were true, then the inhibition of NO synthase in the NTS would have
selectively affected the regulation of autonomic outflow to the
hindquarter. Because the vasodilator responses produced by systemic
injection of S-nitrosocysteine were
augmented in
prazosin/L-NAME-treated rats, it
is unlikely that the progressive loss of the
L-Glu-mediated hindquarter
vasodilation is due to the diminished vasodilator capacity of
endogenous nitrosyl factors. The exaggerated effects of
S-nitrosocysteine and sodium
nitroprusside in prazosin-treated rats are probably due to the loss of
baroreflex-mediated activation of
1-adrenoceptors that would
normally buffer the vasodilation. The further exaggeration of the
effects of S-nitrosocysteine in the
rats treated with L-NAME and
prazosin is possibly due to the upregulation of the signal transduction
mechanisms by which this S-nitrosothiol relaxes
vascular smooth muscle (see Ref. 22).
In conclusion, the present study has characterized the hemodynamic
responses produced by microinjections of
L-Glu into the NTS of conscious
rats. These microinjections of
L-Glu produced an initial
pressor response and vasoconstriction in peripheral vascular beds via
the activation of sympathetic neurogenic
1-adrenoceptor-mediated processes. The microinjection of
L-Glu also produced a pronounced vasodilation in the hindquarter bed that may be mediated by the release
of preformed pools of nitrosyl factors within the vasculature. As
mentioned, the hindquarter vasodilation may be due to activation of the
lumbar sympathetic vasodilator system, which releases nitrosyl factors.
In further support of this possibility, we have obtained preliminary
evidence that the maximal hindquarter vasodilation produced by the
direct activation of the lumbar sympathetic chain (3.0 V, 20 Hz, 5-ms
duration for 10 s) in pentobarbital-anesthetized rats is unaffected by
the muscarinic receptor antagonist methylatropine (1 mg/kg iv,
n = 5) or the -adrenoceptor
antagonist propranolol (1 mg/kg iv, n = 5). At present, we are not certain whether the neurogenic vasodilator
system is a "final common pathway" for vasodilation in the
hindquarter bed or, rather, is activated only by specific stimuli.
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ACKNOWLEDGEMENTS |
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This work was supported by National Heart, Lung, and Blood Institute Grants HL-32205 and HL-143888, a Merit Review and Career Award through the Department of Veterans Affairs, Conselho Nacional de Pesquisa (CNPq-520059/96-2), and Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP-96/6075-5).
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FOOTNOTES |
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Address for reprint requests: E. Colombari, Dept. of Physiology, UNIFESP-Escola Paulista de Medicina, Sao Paulo-SP 04023-900, Brazil (e-mail: COLOMBARI{at}fisiocardio.epm.br).
Received 13 November 1997; accepted in final form 18 December 1997.
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REFERENCES |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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) from baseline.
* P < 0.05, significant
response; 
P < 0.05, significant change from Pre values.
