| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
The present study sought to
determine whether arterial baroreceptor afferents mediate the
inhibitory effect of an acute increase in arterial blood pressure (AP)
on thirst stimulated by systemically administered ANG II or by
hyperosmolality. Approximately 2 wk after sinoaortic denervation, one
of four doses of ANG II (10, 40, 100, or 250 ng · kg
1 · min1) was
infused intravenously in control and complete sinoaortic-denervated (SAD) rats. Complete SAD rats ingested more water than control rats
when infused with 40, 100, or 250 ng · kg1 · min1 ANG II.
Furthermore, complete SAD rats displayed significantly shorter
latencies to drink compared with control rats. In a separate group of
rats, drinking behavior was stimulated by increases in plasma
osmolality, and mean AP was raised by an infusion of phenylephrine (PE). The infusion of PE significantly reduced water intake and lengthened the latencies to drink in control rats but not in complete SAD rats. In all experiments, drinking behavior of rats that were subjected to sinoaortic denervation surgery but had residual
baroreceptor reflex function (partial SAD rats) was similar to that of
control rats. Thus it appears that arterial baroreceptor afferents
mediate the inhibitory effect of an acute increase in AP on thirst
stimulated by ANG II or hyperosmolality.
water intake; angiotensin II; hyperosmolality
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
ACCUMULATING EVIDENCE INDICATES that an acute increase in arterial blood pressure (AP) inhibits thirst. Initial observations by Evered and colleagues (3, 4, 17) demonstrated that cumulative water intakes in rats were greater when the increase in AP evoked by an intravenous infusion of ANG II was prevented by cotreatment with one of three vasodilators [isoproterenol, diazoxide (DZX), or minoxidil]. With each dose of ANG II tested and all three vasodilators used, attenuation of the ANG II-induced increase in AP resulted in a greater cumulative water intake (3, 4, 17). Similar observations have been reported in dogs (13). Recently, we confirmed those findings and also demonstrated that an acute increase in AP inhibits drinking behavior stimulated by hyperosmolality or hypovolemia in rats (21). With all three stimuli for thirst, an acute increase in AP resulted in a reduction of water intake and a longer latency to drink. Furthermore, this inhibitory effect of an increase in AP on thirst appeared to be graded; small increases in AP resulted in small reductions in water intake and longer latencies to drink, whereas large increases in AP resulted in larger reductions in water intake and even longer latencies to drink (21).
The primary way in which the central nervous system detects acute perturbations in AP is through an afferent signal arising from stretch receptors located on the vessel walls of the aortic arch and carotid sinus (arterial baroreceptors). Previous studies attempting to remove arterial baroreceptor afferents have not observed potentiated water intakes evoked by peripherally administered ANG II (10, 16). However, it is not clear whether the baroreceptor afferents of the animals in these studies were completely eliminated, as discussed previously (21). On the other hand, complete elimination of both arterial and cardiopulmonary baroreceptor afferents, by surgical denervation in dogs (11) or electrolytic lesions of the nucleus tractus solitarius (NTS) in rats (18), results in greater water intake and shorter latency to drink during an intravenous infusion of pressor doses of ANG II. Therefore, the inhibitory effect of an acute increase in AP may be mediated by both cardiopulmonary and arterial baroreceptors. However, because no study has convincingly evaluated the contribution of arterial baroreceptors to the AP-evoked inhibition of thirst stimulated by peripherally administered ANG II, it is unclear whether one or both types of afferents mediate this inhibition. Therefore, we sought to reinvestigate whether complete removal of arterial baroreceptor afferents eliminates the inhibition of drinking behavior resulting from an acute increase in AP.
In the present experiments, sinoaortic-denervated (SAD) rats plus nonsurgical controls were infused intravenously with several doses of ANG II. If arterial baroreceptors mediate the inhibition of drinking behavior during an acute increase in AP, then complete SAD rats should drink sooner and ingest more water compared with weight-matched control rats during an intravenous infusion of pressor doses of ANG II. In addition, we sought to determine whether complete removal of arterial baroreceptor afferents would eliminate the inhibition of thirst observed during increases in AP when drinking behavior was stimulated by hyperosmolality. Thus SAD rats and weight-matched controls were infused with hypertonic saline (HS) to raise plasma osmolality (Posmol), and AP was raised by an infusion of phenylephrine (PE). In all experiments, partial SAD rats also were studied to determine whether drinking responses of these rats were affected by an increase in AP, like control rats.
| |
METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Animals. Adult male Sprague-Dawley rats (Zivic Laboratories, Zelienople, PA) were individually housed in a temperature-controlled room (22-23°C) with a 12:12-h light-dark cycle (lights on at 8:00 AM). Tap water and Purina Laboratory Chow (no. 5001) were available ad libitum except where noted. All experiments began between 10:00 AM and 2:00 PM. At least 24 h before baroreflex testing, catheters were implanted in the left femoral artery (Silastic or Microrenthane tubing; Braintree Scientific) and vein (PV-3 tubing) using halothane as anesthesia (2-3% in 100% O2). All catheters were tunneled subcutaneously to exit between the scapulae and were filled with heparinized saline (arterial, 1,000 U/ml; venous, 40 U/ml). Rats were fitted with an infusion harness (Harvard Apparatus) that allowed the catheters to pass outside the cage while protected by a steel spring.
At least 1 h before experiments began, rats were weighed and returned to wire mesh cages with urine collection funnels attached to the bottom. Food was removed, and a 50-ml burette containing tap water was placed on the cage except where noted. AP was recorded by connecting the arterial line to a Statham pressure transducer (Grass Instruments, Quincy, MA) and a polygraph chart recorder (model 7; Grass Instruments). The pulsatile AP signal was electronically filtered to obtain mean AP (MAP). Heart rate (HR) was obtained through a tachograph (model 7P44; Grass Instruments) triggered by the pulsatile AP. During drinking experiments, MAP and HR values for each time point were computed as an average of three values taken 10 s apart. Because the act of drinking has been reported to increase MAP and HR (8), MAP and HR values were not taken during a drinking bout, but values were collected at the closest minute to the drinking bout.Sinoaortic denervation. Approximately 2 wk before baroreflex testing and initiation of drinking experiments, sinoaortic denervation was performed using halothane as anesthesia (2-3% in 100% O2), as described previously (12, 19). Briefly, the superior cervical ganglion was removed, and the superior laryngeal nerve was sectioned at its junction with the vagus nerve. The common carotid artery, carotid bifurcation, and internal and external carotid arteries were stripped of neural and connective tissue and swabbed with 10% phenol in ethanol. After surgery, rats were injected with either hexamethonium (30 mg/kg sc) or atropine (0.1 mg/kg sc) two times daily for 2 days and with antibiotic (Dual-Cillin; 30,000 units im). Because water intake usually decreases after sinoaortic denervation, rats also were given daily injections of isotonic saline (SLN, 15 ml sc) until spontaneous drinking resumed.
Baroreflex testing. The completeness of the sinoaortic denervation was assessed by observing changes in HR in response to intravenous bolus injections of PE (4 µg/kg) and sodium nitroprusside (SNP; 4 µg/kg), as described previously (19). To verify that cardiac afferents were not affected by these surgical denervations, rats were tested additionally for MAP and HR responses to the 5-HT3 5-hydroxytryptamine agonist phenyl biguanide (PBG; 25 µg/kg iv). All baroreflex testing was performed in awake, freely-moving rats. Each rat was tested at least three times for AP and HR responses to PE, SNP, and PBG, and peak changes in each variable were averaged across trials. A denervation was considered to be complete when the change in HR in response to PE and SNP was 0 beats/min; such rats will be referred to as "complete SAD rats." Rats that underwent these surgical denervations but still had residual baroreceptor reflex function will be referred to as "partial SAD rats." In addition, "control" rats consisted of weight-matched rats that did not undergo sinoaortic denervation surgery. Baseline MAP was calculated as an average of values taken every 20 s for 5 min immediately before baroreflex testing. Lability of MAP was calculated as the standard deviation of the mean.
Effect of sinoaortic denervation on drinking behavior during an
infusion of ANG II.
After a 20-min baseline recording of MAP and HR, complete SAD
(n = 5), partial SAD (n = 5-10),
and control (n = 8) rats were infused intravenously
with one of four doses of ANG II (10, 40, 100, or 250 ng · kg1 · min1; 25 µl/min) for 60 min using an infusion pump (model A-99; Razel). Experiments were performed every other day, and the infusion dose of
ANG II was randomized. In initial experiments, two complete SAD rats
were tested for drinking responses to only 10 and 100 ng · kg1 · min1 ANG II. The
results from these rats were combined with the results from five other
complete SAD rats infused with 10, 40, 100, and 250 ng · kg1 · min1 ANG II.
Effect of intravenous infusions of ANG II on plasma ANG II
levels.
To determine the plasma ANG II levels resulting from the infusion of
ANG II, a separate group of control rats (n = 8) was infused with ANG II (10, 40, 100, and 250 ng · kg1 · min1; 25 µl/min). In addition, a subset (n = 4) of complete
SAD rats used in the above drinking studies was infused with 40 and 100 ng · kg1 · min1 ANG II for
determination of plasma ANG II levels. In each animal, blood samples
(0.5 ml) were collected from the arterial catheter into microcentrifuge
tubes containing 3 mM EDTA (15 µl) and 20 mM 1,10-phenanthroline (45 µl) at baseline and at 3, 15, and 45 min after the initiation of the
ANG II infusion. Samples were centrifuged immediately (10,000 g, 1 min), and the plasma was stored at 
80°C until ANG
II levels were determined by RIA, as described previously
(22). In this and subsequent experiments, the first blood
sample was replaced with an equal volume of SLN injected intravenously,
whereas subsequent samples were replaced with red blood cells
from the previous sample resuspended in heparinized saline (40 U/ml).
80°C until plasma ANG II
levels were determined by RIA.
Effects of sinoaortic denervation on the AP-evoked inhibition of
drinking behavior during increases in Posmol.
One hour before experiments, food and water were removed from the
cages. After a 20-min baseline recording of MAP and HR, rats were
infused with HS (1 M NaCl, 2 ml/h) for 2 h. At the end of the 2-h
period, the infusions were switched either to PE (4 µg · kg1 · min1), to
increase AP, or to SLN (1.5 ml/h) for the next 90 min. Control (n = 8), partial SAD (n = 5), and
complete SAD (n = 5) rats were subjected to both the PE
and SLN protocols separated by 3 days, and the order was randomized.
Statistical analysis. All data are expressed as means ± SE. Body weight, baseline MAP and lability, and baroreflex responses were analyzed by ANOVA (Systat; SPSS) followed by a Fisher's post hoc test. Baroreflex gain was calculated by dividing the absolute change in HR by the change in MAP.
Water intakes, MAP, and HR were analyzed by a two-way ANOVA with repeated measures. Latencies to drink were analyzed similarly, but only rats that drank during the test were used in the analysis. When significant F values were obtained for the group or dose factor, one-way ANOVA was performed at each time followed by a Fisher's or layered Bonferroni post hoc test, respectively. The repeated-measures variable was analyzed by a repeated-measures ANOVA followed by paired t-tests with layered Bonferroni correction to compare each time with baseline values. Urine volume, urinary Na+ and K+ excretion, and Posmol were analyzed similarly. The percentages of rats that drank during each experiment were compared between treatments and within each group by a Fisher's Exact Test. When water intake or latency to drink was plotted as a function of baroreflex gain, the distribution of complete SAD rats vs. partial SAD or control rats was compared by a Fisher's Exact Test. A horizontal line was drawn just below the lowest water intake or just above the longest latency to drink among the complete SAD rats, and the numbers of rats above and below the line were compared with the numbers of partial SAD or control rats situated similarly. Rats that did not drink were assigned latencies to drink of 60 min for purposes of comparison. Plasma ANG II levels were log transformed and analyzed by one-way repeated-measures ANOVA followed by appropriate post hoc testing as described above. Plasma ANG II levels in complete SAD rats and control rats infused with 40 and 100 ng · kg1 · min1 ANG II were
compared by a two-way ANOVA with repeated measures. Plasma ANG II
levels associated with experimental models known to induce thirst were
compared with baseline values by independent t-tests. These
plasma ANG II levels also were compared by independent t-tests with plasma ANG II levels at 15 min after each
infusion dose of ANG II.
In all statistical comparisons, a P value <0.05 was
considered to be significant.
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Effect of sinoaortic denervation on drinking behavior during an
infusion of ANG II.
Baroreflex responses to PE, SNP, and PBG for complete SAD, partial SAD,
and control rats are presented in Table
1. Baseline MAP and HR were not different
between groups (Table 1; P > 0.8 from overall ANOVAs),
and MAP of complete SAD rats was significantly more labile than that of
control or partial SAD rats (Table 1), as reported previously
(20, 25). By definition, complete SAD rats displayed no
change in HR to intravenous bolus injection of PE and SNP. Furthermore,
complete SAD rats had a greater change in MAP in response to PE and SNP
than control rats did, presumably because of a loss of baroreflex
buffering. Partial SAD rats displayed HR changes in response to PE and
SNP that were significantly smaller than those in control rats but
significantly greater than those in complete SAD rats (Table 1).
Complete SAD and partial SAD rats displayed bradycardic and hypotensive
responses to the PBG that were not different from those of control rats
(Table 1).
|
1 · min1 ANG II,
complete SAD rats ingested significantly more water compared with
control or partial SAD rats during the 60-min test (Figs. 1 and
2A). Furthermore, complete SAD rats displayed significantly shorter latencies to drink compared with control or partial SAD rats
infused with 100 and 250 ng · kg1 · min1 ANG II
(Fig. 2B). Although latencies to drink were not
statistically significant between groups at 40 ng · kg1 · min1 ANG II, a
greater percentage of complete SAD rats drank during the 60-min test
compared with control or partial SAD rats given this dose (Table
2). No differences were observed in water
intakes or latency to drink between the three groups during the
infusion of 10 ng · kg1 · min1 ANG II.
|
|
|
1 · min1 ANG II
plotted as a function of baroreflex gain from the PE baroreflex test
are presented in Fig. 3 and show the
importance of studying complete SAD rats. By definition, all complete
SAD rats had a baroreflex gain equal to zero, and the majority of these
rats ingested more water compared with control rats at both 40 and 100 ng · kg1 · min1 ANG II
(Fig. 3). Although the baroreflex gain was significantly blunted in
every partial SAD rat compared with control rats, partial SAD rats
usually drank less water than complete SAD rats but similar amounts of
water as control rats when infused with 40 and 100 ng · kg1 · min1 ANG II
(Fig. 3). Similarly, complete SAD rats generally drank sooner than
control or partial SAD rats infused with 40 and 100 ng · kg1 · min1 ANG II
(Fig. 3).
|
1 · min1 ANG II
produced significant increases in MAP of complete SAD, partial SAD, and
control rats (Fig. 4). Each of these
infusion doses of ANG II produced greater elevations in MAP in complete
SAD rats than in control rats (P < 0.05; Fig. 4).
Compared with control rats, partial SAD rats also showed an exaggerated
pressor response to ANG II (P < 0.05); however,
complete SAD rats displayed significantly higher MAP values than
partial SAD rats infused with 40 and 100 ng · kg1 · min1 ANG II
at 3 and 15 min (P < 0.05).
|
1 · min1 ANG II
caused significant decreases in HR in control rats throughout the
60-min test (Fig. 5). In contrast, these
ANG II infusions significantly increased HR above baseline values in
complete SAD rats (Fig. 5), whereas the HR of partial SAD rats remained
unchanged from baseline values with each dose of ANG II. The infusion
of 10 ng · kg1 · min1 ANG
II did not alter MAP or HR in any group (Figs. 4 and 5).
|
|
Effect of intravenous infusion of ANG II on plasma ANG II levels.
Each dose of ANG II tested in control rats (10, 40, 100, and 250 ng · kg1 · min1) produced a
significant and sustained increase in plasma ANG II levels above
baseline values (Fig. 6A). As
the dose increased, plasma ANG II levels were significantly greater
than those during the next lower dose of ANG II at every time point.
Similarly, infusion of 40 and 100 ng · kg1 · min1 ANG II in
complete SAD rats significantly increased plasma ANG II levels above
baseline values throughout the infusion period (Fig. 6A),
and these levels did not differ from the elevated levels in control
rats at any time (P > 0.4).
|
1 · min1 ANG II
(P > 0.4), and 48 h of water deprivation were not
significantly different from 40 ng · kg1 · min1 ANG II
(P > 0.3). However, plasma ANG II levels after 24 and 48 h of water deprivation were significantly lower than the levels observed during the two higher doses of ANG II tested. Indeed, plasma
ANG II levels during 100 and 250 ng · kg1 · min1 ANG II were
much greater than plasma ANG II levels after any of the treatments
examined (Fig. 6).
Effects of sinoaortic denervation on the AP-evoked inhibition of drinking behavior during increases in Posmol. Baroreflex responses for control, partial SAD, and complete SAD rats used in the hyperosmolality experiments are presented in Table 1 and are similar to those discussed above for ANG II experiments. Again, baseline MAP and HR were not different between groups (Table 1; P > 0.2 from overall ANOVAs), and MAP of complete SAD rats was significantly more labile than that of control or partial SAD rats (Table 1).
Control rats treated with HS + SLN drank significant amounts of water and displayed a short latency to drink (3.0 ± 0.4 min). In agreement with previous findings (21), an infusion of PE significantly increased MAP above baseline values and inhibited drinking behavior. Control rats treated with HS + PE ingested significantly less water than control rats treated with HS + SLN (Fig. 7) and displayed a significantly longer latency to drink than those treated with HS + SLN (7.8 ± 1.7 vs. 3.0 ± 0.4 min, respectively; P < 0.05). Furthermore, a significantly smaller percentage of control rats treated with HS + PE drank during the test compared with control rats treated with HS + SLN (Table 4).
|
|
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
An acute increase in AP has been demonstrated to inhibit thirst stimulated by ANG II, hyperosmolality, or hypovolemia in rats (3, 4, 13, 17, 21). However, the afferent signal(s) mediating this inhibitory effect has not been established. The primary finding of the present study is that sinoaortic denervation eliminates the inhibition of thirst resulting from an acute increase in AP. Complete SAD rats drank sooner and ingested more water compared with control rats (or partial SAD rats) during an intravenous infusion of ANG II. Similarly, PE-induced increases in AP failed to inhibit drinking behavior in complete SAD rats that were infused intravenously with HS. Thus it appears that arterial baroreceptors play a critical role in mediating the inhibition of thirst during an acute increase in AP.
Complete SAD enhances drinking behavior during an infusion of ANG II. The primary way by which the central nervous system detects changes in AP is through an afferent neural signal arising from arterial baroreceptors. Because removal of these afferent nerves eliminates the reflexive changes in sympathetic nerve activity and HR to changes in AP (1, 2, 27), we hypothesized that complete removal of these afferents would eliminate the pressure-dependent inhibition of thirst during an intravenous infusion of ANG II. Although previous reports suggest that sinoaortic denervation does not alter water intakes stimulated by peripherally administered ANG II (10, 16), the SAD rats in those studies may not have been completely denervated, as discussed below. On the other hand, complete removal of both arterial and cardiopulmonary afferents, by surgical denervation in dogs (11) or electrolytic lesion of NTS in rats (18), resulted in greater water intakes and shortened latencies to drink during intravenous infusions of pressor doses of ANG II. Therefore, arterial and/or cardiopulmonary stretch receptors mediate the AP-evoked inhibition of drinking behavior during an infusion of ANG II, but it was unclear whether one or both types of afferents mediate this inhibition.
In the present study, complete sinoaortic denervation resulted in significantly shorter latencies to drink and greater water intakes during an infusion of pressor doses of ANG II, thereby suggesting that arterial baroreceptors play a critical role in mediating the inhibition of thirst during an acute increase in AP. If arterial baroreceptors predominantly mediate this inhibition, then the latencies to drink and water intakes of complete SAD rats should be similar to those observed in rats when the ANG II-induced increase in AP was attenuated with a vasodilator (4, 17, 21). Indeed, a comparison of the present data with our recently published findings, using the same general procedures as in the present study (21), confirms this hypothesis. Complete SAD rats infused with 100 ng · kg1 · min1 ANG II and
control rats (n = 8) infused with 100 ng · kg1 · min1 ANG II plus
intravenous administration of DZX (10 mg/kg iv) display similar
latencies to drink (9.3 ± 1.1 vs. 8.0 ± 1.2 min,
respectively; P > 0.4) and ingest similar amounts of
water during a 60-min test (8.3 ± 1.0 vs. 8.2 ± 0.7 ml,
respectively, P > 0.9). Therefore, the surgical
elimination of the neural afferent signal associated with an acute
increase in AP by complete sinoaortic denervation has the same effect
on drinking behavior stimulated by an intravenous infusion of ANG II as
the pharmacological elimination of the acute increase in AP in intact
rats. These observations suggest that the AP-evoked inhibition of
drinking behavior is mediated by arterial baroreceptor afferents.
Although a large increase in AP can elevate cardiac pressure and
stimulate mechanosensitive cardiac afferents (6), the shortened latencies and greater water intakes in our complete SAD rats
cannot be attributed to the destruction of cardiopulmonary afferents.
First, complete SAD rats exhibited normal hypotensive and bradycardic
responses to PBG, a response that is dependent on intact
cardiopulmonary afferents (26). Second, the water intakes
of complete SAD rats are similar to those of NTS-lesioned rats studied
previously in a similar protocol in this laboratory (8.3 ± 1.0 vs. 10.3 ± 0.7 ml, respectively; P > 0.1; see
Ref. 18), despite the fact that NTS lesions eliminate
neural input from cardiopulmonary and other visceral afferents. Thus it
appears that arterial baroreceptors solely mediate the inhibition of
thirst resulting from an increase in AP during an infusion of ANG II.
Drinking behavior in partial SAD rats during an infusion of ANG II.
One of the most striking observations regarding the effect of
sinoaortic denervation on ANG II-evoked thirst was the requirement that
the denervation be complete. In the present study, a denervation was
considered to be complete only when there were no reflexive changes in
HR during intravenous bolus injections of PE and SNP. Those SAD rats
exhibiting residual HR responses during baroreflex testing were
classified as partial SAD rats; these rats displayed changes in HR of
10-30 beats/min compared with 50-95 beats/min in control rats
in response to PE and SNP. With each dose of ANG II tested, partial SAD
rats displayed latencies to drink and ingested amounts of water similar
to those of weight-matched control rats (see Fig. 3). Even partial SAD
rats displaying a baroreflex gain of <0.5
beats · min1 · mmHg1 drank
water in amounts similar to control rats during infusions of 40 or 100 ng · kg1 · min1 ANG II (see
Fig. 3). The critical importance of a complete sinoaortic denervation
in studies assessing the role of arterial baroreceptor afferents has
been emphasized previously (20), and the present results
reinforce this point.
Cardiovascular responses to ANG II in SAD rats.
An intravenous infusion of 40, 100, and 250 ng · kg1 · min1 ANG II
produced significant increases in MAP and decreases in HR in control
rats. In contrast, complete SAD rats displayed greater elevations in
MAP and a significant tachycardia throughout the test. Similar
increases in HR during an infusion of ANG II have been reported in
baroreceptor-denervated dogs (5, 7) and rats
(18). This response likely results from direct
chronotropic effects of ANG II via AT1 receptors
(14) and an increase in sympathetic outflow (5, 14,
27). On the other hand, the HR of partial SAD rats infused with
ANG II did not change from baseline values, which probably results from
a small residual baroreflex-induced bradycardia being cancelled by the
tachycardic effects of ANG II. The larger increase in AP observed
during the ANG II infusion in partial and complete SAD rats compared
with control rats most likely results from the blunting or loss of baroreceptor-mediated sympathoinhibition and an increase in cardiac output.
Physiological significance of plasma ANG II levels.
The enhancement of thirst stimulated by the infusion of ANG II in
complete SAD rats cannot be explained by differences in plasma ANG II
levels because complete SAD and control rats exhibited similar
sustained increases in plasma ANG II levels during infusion of 40 or
100 ng · kg1 · min1 ANG II.
In agreement with previous studies (9, 15), the increases
in plasma ANG II levels produced by the larger infusion doses of ANG II
do not resemble the plasma ANG II levels produced by any treatment
examined in the present study; however, the increase in plasma ANG II
levels observed during infusion of 40 ng · kg1 · min1 ANG II was
similar to that observed after 48 h of water deprivation (see Fig.
6). Because the enhancement of drinking behavior during an infusion of
ANG II was observed in complete SAD rats at this dose, the present
results suggest that arterial baroreceptors are capable of influencing
drinking behavior in association with physiological increases in plasma
ANG II levels.
Sinoaortic denervation eliminates AP-evoked inhibition of drinking behavior during increases in Posmol. Previously, we reported that increases in AP lengthen the latency to drink and reduce water intake stimulated by increases in Posmol and that this inhibitory effect is related to the evoked increase in AP in the range of ~100 to ~160 mmHg (21). The present study confirms those findings but also demonstrates that complete SAD rats treated with HS + PE behave similarly to control rats treated with HS + SLN despite significant differences in MAP in the two groups. These effects cannot be attributed to differences in Posmol, urinary excretion of the Na+ load, or differences in MAP between complete SAD and control rats. Furthermore, complete SAD rats treated with HS + SLN displayed similar latencies to drink and ingested comparable amounts of water as control rats treated with HS + SLN, thereby suggesting that complete SAD rats are not more sensitive to the hyperosmotic signal for thirst. Again, the degree of the denervation was critical for the elimination of this inhibitory effect; partial SAD rats treated with HS + PE displayed latencies to drink and water intakes that were not different from control rats treated with HS + PE (see Fig. 7). Thus arterial baroreceptors mediate AP-evoked inhibition of thirst regardless of whether drinking behavior is stimulated by hyperosmolality or by peripherally administered ANG II.
Drinking behavior and the baroreceptor reflex.
When water intake is plotted as a function of MAP, the relationship
resembles the well-known baroreceptor reflex curve relating changes in
HR or sympathetic nerve activity to changes in MAP (21).
As MAP increased, water intake decreased whether it was stimulated by
ANG II, hyperosmolality, or hypovolemia in rats. Furthermore, this
inhibitory effect was directly related to the increase in AP in the
range of ~100 to ~160 mmHg and appeared to be equivalent across
these three thirst stimuli (21). Because complete removal
of arterial baroreceptor afferents is known to eliminate the reflexive
changes in HR or sympathetic nerve activity during acute increases in
AP (1, 2, 27), it seemed plausible that complete removal
of these same afferents would eliminate the inhibitory effect of an
acute increase in AP on drinking behavior. As expected, when water
intakes of complete SAD rats infused with 100 ng · kg1 · min1 ANG II are
expressed as a percentage of the water intakes of control rats infused
with 100 ng · kg1 · min1
ANG II plus DZX (10 mg/kg iv), water intakes of complete SAD rats were
equivalent to those of control rats infused with 100 ng · kg1 · min1 ANG II plus
DZX (10 or 20 mg/kg iv) despite significant differences in MAP (Fig.
8A). Similarly, water intakes
of complete SAD rats treated with HS + PE were equivalent to control or
complete SAD rats treated with HS + SLN (Fig. 8B) despite
significant differences in MAP. With both ANG II and hyperosmolality,
the water intakes of partial SAD rats with an elevated AP were
equivalent to control rats with a similar increase in MAP. Therefore,
complete removal of arterial baroreceptor afferents eliminates the
AP-evoked inhibitory influence on drinking behavior when stimulated by
ANG II or hyperosmolality.
|
Perspectives
The baroreflex plays an important role in maintaining proper perfusion of tissues when animals are faced with perturbations in AP. Changes in AP are sensed by stretch receptors, relayed through a neural afferent signal to the central nervous system, and evoke changes in the activity of sympathetic and parasympathetic nervous systems as well as hypothalamic endocrine systems (24). During an increase in AP, these reflex responses include decreases in cardiac output, vascular resistance, and firing rate of putative vasopressin neurons. In addition, an increase in AP leads to an increase in the renal excretion of water and Na+ thereby decreasing intravascular volume and restoring AP. All of these responses act in concert to restore AP toward original levels. In an analogous manner, perturbations in AP might be expected to limit the ingestion of water and Na+, thereby aiding in the restoration of AP. Indeed, we have previously demonstrated that acute increases in AP inhibit drinking behavior stimulated by ANG II, hyperosmolality, and hypovolemia in rats (21). Similar to the effects of complete removal of arterial baroreceptor afferents on reflexive changes in sympathetic nerve activity and HR during acute changes in AP (1, 2, 27), the present study demonstrates that complete sinoaortic denervation eliminated the inhibitory effect of acute increases in AP on drinking behavior. Therefore, influences of baroreceptors on cardiovascular homeostasis should include behavioral responses in addition to neural, endocrine, and renal responses.| |
ACKNOWLEDGEMENTS |
|---|
We thank Ruwani Bandaranayake and Jason Devlin for technical assistance and Dr. Ian Reid for the generous gift of the ANG II antibody.
| |
FOOTNOTES |
|---|
This research was supported by National Institutes of Health Grants MH-25140 (E. M. Stricker) and HL-55687 (A. F. Sved). S. D. Stocker was supported by an Andrew Mellon Predoctoral Fellowship.
Present address for S. D. Stocker: Dept. of Physiology, Univ. of Texas Health Sciences Center-San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229.
Address for reprint requests and other correspondence: A. F. Sved, Dept. of Neuroscience, Univ. of Pittsburgh, 446 Crawford Hall, Pittsburgh, PA 15260 (E-mail: sved{at}bns.pitt.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
10.1152/ajpregu.00651.2001
Received 2 November 2001; accepted in final form 18 January 2002.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Dorward, PK,
Bell LB,
and
Rudd CD.
Cardiac afferents attenuate renal sympathetic baroreceptor reflexes during acute hypertension.
Hypertension
16:
131-139,
1990
2.
Dorward, PK,
Riedel W,
Burke SL,
Gipps J,
and
Korner PI.
The renal sympathetic baroreflex in the rabbit. Arterial and cardiac baroreceptor influences, resetting, and effect of anesthesia.
Circ Res
57:
618-633,
1985
3.
Evered, MD.
Investigating the role of angiotensin II in thirst: interactions between arterial pressure and the control of drinking.
Can J Physiol Pharmacol
70:
791-797,
1992[Web of Science][Medline].
4.
Evered, MD,
Robinson MM,
and
Rose PA.
Effect of arterial pressure on drinking and urinary responses to angiotensin II.
Am J Physiol Regulatory Integrative Comp Physiol
254:
R69-R74,
1988
5.
Fujii, AM,
and
Vatner SF.
Direct versus indirect pressor and vasoconstrictor actions of angiotensin in conscious dogs.
Hypertension
7:
253-261,
1985
6.
Hainsworth, R.
Reflexes from the heart.
Physiol Rev
71:
617-658,
1991
7.
Heyndrickx, GR,
Boettcher DH,
and
Vatner SF.
Effects of angiotensin, vasopressin, and methoxamine on cardiac function and blood flow distribution in conscious dogs.
Am J Physiol
231:
1579-1587,
1976
8.
Hoffman, WE,
Phillips MI,
Wilson E,
and
Schmid PG.
A pressor response associated with drinking in rats.
Proc Soc Exp Biol Med
154:
121-124,
1977[Medline].
9.
Johnson, AK,
Mann JF,
Rascher W,
Johnson JK,
and
Ganten D.
Plasma angiotensin II concentrations and experimentally induced thirst.
Am J Physiol Regulatory Integrative Comp Physiol
240:
R229-R234,
1981
10.
Kadekaro, M,
Creel M,
Terrell ML,
Lekan HA,
Gary Jr HE,
and
Eisenberg HM.
Effects of sinoaortic denervation on glucose utilization in the subfornical organ and pituitary neural lobe during administration of angiotensin II.
Peptides
10:
103-108,
1989[Web of Science][Medline].
11.
Klingbeil, CK,
Brooks VL,
Quillen Jr EW,
and
Reid IA.
Effect of baroreceptor denervation on stimulation of drinking by angiotensin II in conscious dogs.
Am J Physiol Endocrinol Metab
260:
E333-E337,
1991
12.
Krieger, EM.
Neurogenic hypertension in the rat.
Circ Res
15:
511-521,
1964
13.
Kucharczyk, J.
Inhibition of angiotensin-induced water intake following hexamethonium pretreatment in the dog.
Eur J Pharmacol
148:
213-219,
1988[Web of Science][Medline].
14.
Li, Q,
Zhang J,
Pfaffendorf M,
and
van Zwieten PA.
Direct positive chronotropic effects of angiotensin II and angiotensin III in pithed rats and in rat isolated atria.
Br J Pharmacol
118:
1653-1658,
1996[Web of Science][Medline].
15.
Mann, JF,
Johnson AK,
and
Ganten D.
Plasma angiotensin II: dipsogenic levels and angiotensin-generating capacity of renin.
Am J Physiol Regulatory Integrative Comp Physiol
238:
R372-R377,
1980
16.
Rettig, R,
and
Johnson AK.
Aortic baroreceptor deafferentation diminishes saline-induced drinking in rats.
Brain Res
370:
29-37,
1986[Web of Science][Medline].
17.
Robinson, MM,
and
Evered MD.
Pressor action of intravenous angiotensin II reduces drinking response in rats.
Am J Physiol Regulatory Integrative Comp Physiol
252:
R754-R759,
1987
18.
Schreihofer, AM,
Stricker EM,
and
Sved AF.
Nucleus of the solitary tract lesions enhance drinking, but not vasopressin release, induced by angiotensin.
Am J Physiol Regulatory Integrative Comp Physiol
279:
R239-R247,
2000
19.
Schreihofer, AM,
and
Sved AF.
Nucleus tractus solitarius and control of blood pressure in chronic sinoaortic denervated rats.
Am J Physiol Regulatory Integrative Comp Physiol
263:
R258-R266,
1992
20.
Schreihofer, AM,
and
Sved AF.
Use of sinoaortic denervation to study the role of baroreceptors in cardiovascular regulation.
Am J Physiol Regulatory Integrative Comp Physiol
266:
R1705-R1710,
1994
21.
Stocker, SD,
Stricker EM,
and
Sved AF.
Acute hypertension inhibits thirst stimulated by ANG II, hyperosmolality, or hypovolemia in rats.
Am J Physiol Regulatory Integrative Comp Physiol
280:
R214-R224,
2001
22.
Stocker, SD,
Sved AF,
and
Stricker EM.
Role of renin-angiotensin system in hypotension-evoked thirst: studies with hydralazine.
Am J Physiol Regulatory Integrative Comp Physiol
279:
R576-R585,
2000
23.
Stornetta, RL,
Guyenet PG,
and
McCarty RC.
Autonomic nervous system control of heart rate during baroreceptor activation in conscious and anesthetized rats.
J Auton Nerv Syst
20:
121-127,
1987[Web of Science][Medline].
24.
Sved, AF.
Cardiovascular system.
In: Fundamental Neuroscience, edited by Zigmond MJ,
Bloom FE,
Landis SC,
Roberts JL,
and Squire LR.. New York: Academic, 1999, p. 1051-1062.
25.
Sved, AF,
Schreihofer AM,
and
Kost Jr CK.
Blood pressure regulation in baroreceptor-denervated rats.
Clin Exp Pharmacol Physiol
24:
77-82,
1997[Web of Science][Medline].
26.
Thoren, P.
Role of cardiac vagal C-fibers in cardiovascular control.
Rev Physiol Biochem Pharmacol
86:
1-94,
1979[Medline].
27.
Xu L and Sved AF. Acute sympathoexcitatory action of angiotensin
II in conscious baroreceptor-denervated rats. Am J Physiol
Regulatory Integrative Comp Physiol In press.
This article has been cited by other articles:
|
|
 |
|
  S. C. Malpas, R. Ramchandra, S.-J. Guild, D. M. Budgett, and C. J. Barrett Baroreflex mechanisms regulating mean level of SNA differ from those regulating the timing and entrainment of the sympathetic discharges in rabbits Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R400 - R409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D Stocker and G. M Toney Median preoptic neurones projecting to the hypothalamic paraventricular nucleus respond to osmotic, circulating Ang II and baroreceptor input in the rat J. Physiol., October 15, 2005; 568(2): 599 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Stocker, J. C. Schiltz, and A. F. Sved Acute increases in arterial blood pressure do not reduce plasma vasopressin levels stimulated by angiotensin II or hyperosmolality in rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2004; 287(1): R127 - R137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Stocker, K. J. Keith, and G. M. Toney Acute inhibition of the hypothalamic paraventricular nucleus decreases renal sympathetic nerve activity and arterial blood pressure in water-deprived rats Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2004; 286(4): R719 - R725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Skott Body sodium and volume homeostasis Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2003; 285(1): R14 - R18. [Full Text] [PDF]
|
|
|
|
|
|
S. D. Stocker, C. A. Smith, C. M. Kimbrough, E. M. Stricker, and A. F. Sved Elevated dietary salt suppresses renin secretion but not thirst evoked by arterial hypotension in rats Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2003; 284(6): R1521 - R1528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Bealer Increased dietary sodium alters neural control of blood pressure during intravenous ANG II infusion Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H559 - H565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Xu and A. F. Sved Acute sympathoexcitatory action of angiotensin II in conscious baroreceptor-denervated rats Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2002; 283(2): R451 - R459. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
