Journal of the Autonomic Nervous System, 39 (1992) 97-104
97
© 1992 Elsevier Science Publishers B.V. All rights reserved 0165-1838/92/$05.00 JANS 01279
Effect of nucleus tractus solitarius lesions on cardiovascular responses elicited from the caudal ventrolateral medulla Z.J. G i e r o b a and W.W. Blessing Departments of Medicine and Physiology, Centrefor Neuroscience, Flinders University of South Australia, Bedford Park, Australia (Received 16 December 1991) (Revision received 9 March 1992) (Accepted 11 March 1992)
Key words: Caudal ventrolateral medulla oblongata; Nucleus tractus solitarius; L-Glutamate; GABA; Arterial pressure Abstract Neurons in the caudal ventrolateral medulla (CVLM) which inhibit sympathetic vasomotor tone may have reciprocal connections with the nucleus tractus solitarius (nTS). This study determined whether changes in arterial pressure elicited by chemical excitation or inhibition of neurons in the vasodepressor region of the rabbit CVLM depend on the integrity of the nTS. Unilateral injections of L-glutamate (10 pmol to 100 nmol), or bilateral injections of GABA (1 nmol to 125 nmol), were made into the CVLM, and dose-response effects on arterial pressure determined. The nTS was then bilaterally cauterized, or inhibited by local injections of muscimol, and the dose-response curves were repeated. Neither cauterization nor injection of muscimol significantly altered the slope of the log dose-response curves for L-glutamate, but nTS muscimol increased the fall in arterial pressure for each dose of L-glutamate (P < 0.01). Cauterization of the nTS significantly (P < 0.01) increased the slope of the curve relating dose of GABA to rise in arterial pressure observed, after injection of GABA into the CVLM. This increase in slope was similar to the increase observed when GABA is injected into the CVLM in baroreceptor-denervated rabbits. We conclude that neither the depressor nor the pressor response evoked by stimulation or inhibition of the CVLM is dependent on the integrity of the nTS. Inactivation of the nTS tends to increase the magnitude of the CVLM responses, possibly by removal of baroreceptormediated buffering of the responses.
Introduction
Activation of neurons in the caudal ventrolateral medulla (CVLM) decreases arterial pressure [5,6,9,33]. Neuroinhibitory agents injected into the same region of the medulla increase arterial pressure [5,9,34]. At least some of the vasodepressor neurons appear to act as central inhibitory links
Correspondence to: Z.J. Gieroba, Department of Physiology, Flinders Medical Centre, Bedford Park, SA 5042, Australia.
in the baroreceptor-vasomotor reflex [3,12,14,15, 17,31]. A number of physiological studies have aimed to determine whether axonal projections from perikarya in the ventrolateral medulla modify the manner in which baroreceptor information is processed in the nucleus tractus solitarius (nTS) [1, 11,25,32]. So far there is no consensus concerning any physiological role for these projections. Nevertheless, anatomical studies demonstrate a bidirectional connection between neurons located in the ventrolateral medulla and neurons in the nTS
98 [7,20,23,24,26,27,30]. A possible interaction between axons projecting to the nTS from the ventrolateral medulla, and baroreceptor afferents terminating in the nTS, is suggested by the occurrence of transneuronal transport of Herpes simplex virus from the aortic depressor nerve to perikarya of neurons in the ventrolateral medulla in the rabbit [13]. Approximately 85% of the virus-positive neurons in the CVLM belong to the A1 group of catecholamine-synthesizing neurons. Although these neurons are probably not the vasodepressor neurons [8,28], many hypothalamic-projecting A1 cells are responsive to baroreceptor inputs [16,22], and the collateral axonal projection to the nTS may well have some cardiovascular function in the nTS. The other 15% of CVLM neurons with axonal projections to the nTS may include some of the vasodepressor neurons. The present study was designed to test whether cardiovascular responses elicited from the rabbit CVLM are dependent on the integrity of the nTS, or whether the absence of the nTS might modify the responses. We injected either L-glutamate or G A B A into the CVLM, before and after inactivating the nTS with muscimol-induced pharmacological blockade or with lesions.
Materials and Methods
Experiments were performed on 19 male New Zealand White rabbits (2.5-3 kg), anaesthetised with urethane (1.5 g / k g i.v.). Scopolamine methylbromide (50 /xg/kg, Sigma, MO) was given to minimize airway secretion. Surgical anaesthesia before neuromuscular blockade was judged by the absence of blink and flexor withdrawal response to paw squeeze. The trachea was cannulated, the animal was paralysed with pancuronium bromide (0.5 mg/kg, i.v. initially, with supplemental doses as necessary) and artificially ventilated with oxygen-enriched air, using a Harvard model 681 rodent ventilator. The end-expiratory CO 2 was monitored (Datex Normocap CO 2 monitor, Helsinki, Finland) and maintained at 35-40 mmHg. A polyethylene catheter was inserted into the marginal ear vein for administration of drugs,
and into the left femoral artery for recording of arterial pressure (AP). A Statham P23 ID strain gauge transducer connected to a Grass model 7 polygraph was used to record AP. Mean AP was obtained by filtering the phasic signal. Heart rate (HR) was computed with a Grass 7P4F tachograph triggered by the phasic arterial signal. Body temperature was monitored by a rectal probe and maintained between 38 and 39°C. The head of the rabbit was fixed in a Kopf stereotaxic frame and the medulla was exposed by incision and retraction of the atlantooccipital membrane and removal of the edges of the occipital bone. Neck flexion was adjusted so that the dorsal surface of the medulla was horizontal. The medullary surface was covered with warm Ringer solution. The rostral edge of the area postrema in the midline (obex) served as the stereotaxic zero for the rostro-caudal and medio-lateral coordinates. Scopolamine methylbromide (Sigma, 50 p~g/kg initially with supplemental doses 25 t~g/kg) was administered intravenously every 15 min to block cardiac vagal effects. Intramedullary stereotaxic injections were made through a glass micropipette with bevelled tip (O.D. 20-30 /xm) and long shank. Pharmacological agents were dissolved in Ringer. The volume of each injection (100 nl) was monitored by observing movement of the meniscus in the pipette in response to pressure transmitted from a hand-held syringe. The CVLM injection site was 1 mm caudal to the obex, 3 mm lateral from the midline and 3 mm below the dorsal surface of the medulla. Unilateral injections of L-glutamate (Sigma, 10, 100 pmol, 1, 10, 100 nmol) were made in increasing dose order. In different animals, bilateral injections of GABA (Sigma, 1, 5, 25, 125 nmol) were made, also in increasing dose order. Time between injections was at least 5 min for ~.-glutamate and at least 15 min for GABA. After a dose-response curve to injections of L-glutamate (n = 7 rabbits) or GABA (n = 4 rabbits) was established, the area postrema and the nTS were lesioned using a small-ball type electric cautery. Lesions extended rostrally from the level of nucleus commissuralis, along the edge of fourth ventricle, to the caudal ports. In a separate series of rabbits (n = 5) L-glutamate was injected into
99
the CVLM, the nTS and the area postrema were then inhibited using injections of muscimol (Sigma, 1 nmol in 100 nl of Ringer) at 3 rostrocaudal levels. The first site was 1 mm rostral to the obex, at the lateral edge of fourth ventricle, and 0.5 mm below the dorsal surface of the medulla. The second site was at the lateral edge of the area postrema, at the obex level and 0.5 mm below the dorsal surface of the medulla. The third site was at the level of the nucleus commissuralis, in the midline, 0.3 mm below the dorsal surface of the medulla. An additional injection was made into the area postrema. In three different rabbits dose-response curves to unilateral CVLM injections of L-glutamate or bilateral injections of GABA (doses as above) were established after baroreceptor denervation (bilateral sectioning of the carotid sinus, aortic and vagus nerves). The effectivness of the nTS inactivating procedures, and the baroreceptor denervation was checked by noting that the fall in HR observed after intravenous injection of noradrenaline bitartrate (8 ~ g / k g , Sigma) was markedly reduced or abolished. Horseradish peroxidase (final concentration 1%) was added to the injectate before injections into the CVLM a n d / o r the nTS. After the experiment, the animal was killed with an overdose of pentobarbitone sodium (100 m g/ kg i.v.) and perfused via the heart with buffered formaldehyde/ glutaraldehyde. Transverse sections (50/zm) were made of the medulla and horseradish peroxidase was detected by the diaminobenzidine reaction. Baseline values of AP, HR, and changes of these values were recorded. Data were expressed as mean + S.E.M. Changes in values were compared using linear regression, analysis of variance with repeated measures a n d / o r paired t-test.
Results
Histological verification of microinjection sites within the CVLM showed that injections were centered 1 mm caudal to the obex, between the nucleus ambiguus and the lateral reticular nucleus, where the depressor neurons are located
[18]. The injections of muscimol were within the confines of the nTS, the dorsal motor nucleus of the vagus and the area postrema. The HRP staining spread along the rostrocaudal extent of the nTS, from the commisural nucleus to the pontine portion of the nTS. The nTS lesions extended
Fig. 1. Photomicrographs (left half of each section) and diagrams (right half of each section) of Nissl-stained transverse sections of 3 rostro-caudal levels of medulla (distance from obex on left side) showing the location of lesions of the nTS. Gray shadow area indicates injection site. Abbreviations: IO, inferior olive; LRN, lateral reticular nucleus; MVN, medial vestibular nucleus; nA, nucleus ambiguus; nPH, nucleus prepositus hypoglossi; nTS, nucleus tractus solitarius; py, pyramidal tract; Vsp, spinal nucleus of the trigeminal nerve; XII, hypoglossal nucleus.
100
0"
0.01
Dose of L-glutamate (nmols) 0.1 1 10
100
~5
-10v
-20-
-301 ~ -40~ -50 •" -60
r = 0.88 P 0.05, Fig. 2). Similarly the linear regression between dose of L-glutamate and fall in AP, expressed as percentage changes from baseline, was significant before and after injection of muscimol into the nTS ( P < 0.01) but slopes of the regression lines were not different ( P > 0.05). Similar results were obtained when t.-glutamate was injected into the CVLM before and after cauterization of the nTS. Significant ( P < 0.01) linear regressions between log dose of l.glutamate and fall in AP were observed in both situations but the pre-lesion slope (7.4 mmHg per log dose of L-glutamate) was not significantly ( P > 0.05) different from the post-lesion slope (10.9 mmHg per log dose of L-glutamate), although, as can be seen in Fig. 3, there was a tendency for the responses to be greater after the lesions. Indeed t-tests showed that the falls in AP with 10 and 100 nmol of L-glutamate were significantly higher after the lesions (P < 0.01). Bilateral injection of GABA into the CVLM in animals with intact nTS caused a dose-related increase in AP ( P < 0.01, n = 24 injections in four animals). The slope of the regression line was 4.5 mmHg per log dose of GABA. After nTS
0
Dose of L-glutamate (nmols) 0.1 I 10
0.01
100
-10 .~ -20 m ~a
-30
~ -40
......o
before'e
r = 0.88 P
.......
.........................
~
.~ -50 e,
-60
P < 0.01
-7C Fig. 3. Relationship between the amount of L-glutamate unilaterally injected into the caudal ventrolateral medulla and fall in arterial pressure before and after lesions of the nTS. Linear regression is significant (P 0.05).
101
lesions the corresponding slope was significantly increased (17.3 mmHg per log dose, P < 0.01), as shown in Figs. 4 and 5. The slope of the regression line between dose of GABA and the pressor response expressed as a percentage of the baseline was also significantly greater after the lesions of the nTS (P < 0.01). After baroreceptor denervation the slope of the regression line linking fall in AP to log dose of L-glutamate injected into the CVLM was 6.9 mmHg per log dose of L-glutamate (P < 0.01, n = 20 injections in three animals). This value was unchanged from the slope recorded in non-denervated animals (P > 0.05). The corresponding slope linking a rise in AP to CVLM injection of GABA was 19.2 mmHg per log dose (P < 0.01, n = 16 injections in three animals) and this value
A
was significantly greater (P < 0.01) than the slope of the control regression line.
Discussion The arterial pressure responses evoked by chemical stimulation or inhibition of the CVLM were still present after pharmacological blockade or lesioning of the nTS. The slope of the dose-response curves for L-glutamate and GABA were not reduced by either the nTS lesions or the muscimol injections. The results therefore demonstrate that the cardiovascular effects of alteration of neuronal function in the CVLM are not directly dependent on the integrity of the nTS. Our findings are in keeping with the view
1S01
I'11ASIC ARTERIAL PRESSURE 100 J (ramHg) 50
125sl
MEAN 1501 ARTERIAL PRESSURE100 1 (mmHg) 50 -J
B
15o1
PHASIC ARTERIAL PRESSURE 100 1 (mmHg) 50 J MEAN 150] ARTERIAL PRESSURE100 1 (mmHg) 50 J 1nmol
5 nn'~ol
25nmol
125nmol
Fig. 4. Polygraph records of arterial pressure showing effect of bilateral injections of different amounts of GABA into the caudal ventrolateral medulla before (A) and after (B) lesions of the nTS.
102
~ +90
~ +~o fi
+70 +6O +50 +40.
after lesions r = 0.87 P
97
© 1992 Elsevier Science Publishers B.V. All rights reserved 0165-1838/92/$05.00 JANS 01279
Effect of nucleus tractus solitarius lesions on cardiovascular responses elicited from the caudal ventrolateral medulla Z.J. G i e r o b a and W.W. Blessing Departments of Medicine and Physiology, Centrefor Neuroscience, Flinders University of South Australia, Bedford Park, Australia (Received 16 December 1991) (Revision received 9 March 1992) (Accepted 11 March 1992)
Key words: Caudal ventrolateral medulla oblongata; Nucleus tractus solitarius; L-Glutamate; GABA; Arterial pressure Abstract Neurons in the caudal ventrolateral medulla (CVLM) which inhibit sympathetic vasomotor tone may have reciprocal connections with the nucleus tractus solitarius (nTS). This study determined whether changes in arterial pressure elicited by chemical excitation or inhibition of neurons in the vasodepressor region of the rabbit CVLM depend on the integrity of the nTS. Unilateral injections of L-glutamate (10 pmol to 100 nmol), or bilateral injections of GABA (1 nmol to 125 nmol), were made into the CVLM, and dose-response effects on arterial pressure determined. The nTS was then bilaterally cauterized, or inhibited by local injections of muscimol, and the dose-response curves were repeated. Neither cauterization nor injection of muscimol significantly altered the slope of the log dose-response curves for L-glutamate, but nTS muscimol increased the fall in arterial pressure for each dose of L-glutamate (P < 0.01). Cauterization of the nTS significantly (P < 0.01) increased the slope of the curve relating dose of GABA to rise in arterial pressure observed, after injection of GABA into the CVLM. This increase in slope was similar to the increase observed when GABA is injected into the CVLM in baroreceptor-denervated rabbits. We conclude that neither the depressor nor the pressor response evoked by stimulation or inhibition of the CVLM is dependent on the integrity of the nTS. Inactivation of the nTS tends to increase the magnitude of the CVLM responses, possibly by removal of baroreceptormediated buffering of the responses.
Introduction
Activation of neurons in the caudal ventrolateral medulla (CVLM) decreases arterial pressure [5,6,9,33]. Neuroinhibitory agents injected into the same region of the medulla increase arterial pressure [5,9,34]. At least some of the vasodepressor neurons appear to act as central inhibitory links
Correspondence to: Z.J. Gieroba, Department of Physiology, Flinders Medical Centre, Bedford Park, SA 5042, Australia.
in the baroreceptor-vasomotor reflex [3,12,14,15, 17,31]. A number of physiological studies have aimed to determine whether axonal projections from perikarya in the ventrolateral medulla modify the manner in which baroreceptor information is processed in the nucleus tractus solitarius (nTS) [1, 11,25,32]. So far there is no consensus concerning any physiological role for these projections. Nevertheless, anatomical studies demonstrate a bidirectional connection between neurons located in the ventrolateral medulla and neurons in the nTS
98 [7,20,23,24,26,27,30]. A possible interaction between axons projecting to the nTS from the ventrolateral medulla, and baroreceptor afferents terminating in the nTS, is suggested by the occurrence of transneuronal transport of Herpes simplex virus from the aortic depressor nerve to perikarya of neurons in the ventrolateral medulla in the rabbit [13]. Approximately 85% of the virus-positive neurons in the CVLM belong to the A1 group of catecholamine-synthesizing neurons. Although these neurons are probably not the vasodepressor neurons [8,28], many hypothalamic-projecting A1 cells are responsive to baroreceptor inputs [16,22], and the collateral axonal projection to the nTS may well have some cardiovascular function in the nTS. The other 15% of CVLM neurons with axonal projections to the nTS may include some of the vasodepressor neurons. The present study was designed to test whether cardiovascular responses elicited from the rabbit CVLM are dependent on the integrity of the nTS, or whether the absence of the nTS might modify the responses. We injected either L-glutamate or G A B A into the CVLM, before and after inactivating the nTS with muscimol-induced pharmacological blockade or with lesions.
Materials and Methods
Experiments were performed on 19 male New Zealand White rabbits (2.5-3 kg), anaesthetised with urethane (1.5 g / k g i.v.). Scopolamine methylbromide (50 /xg/kg, Sigma, MO) was given to minimize airway secretion. Surgical anaesthesia before neuromuscular blockade was judged by the absence of blink and flexor withdrawal response to paw squeeze. The trachea was cannulated, the animal was paralysed with pancuronium bromide (0.5 mg/kg, i.v. initially, with supplemental doses as necessary) and artificially ventilated with oxygen-enriched air, using a Harvard model 681 rodent ventilator. The end-expiratory CO 2 was monitored (Datex Normocap CO 2 monitor, Helsinki, Finland) and maintained at 35-40 mmHg. A polyethylene catheter was inserted into the marginal ear vein for administration of drugs,
and into the left femoral artery for recording of arterial pressure (AP). A Statham P23 ID strain gauge transducer connected to a Grass model 7 polygraph was used to record AP. Mean AP was obtained by filtering the phasic signal. Heart rate (HR) was computed with a Grass 7P4F tachograph triggered by the phasic arterial signal. Body temperature was monitored by a rectal probe and maintained between 38 and 39°C. The head of the rabbit was fixed in a Kopf stereotaxic frame and the medulla was exposed by incision and retraction of the atlantooccipital membrane and removal of the edges of the occipital bone. Neck flexion was adjusted so that the dorsal surface of the medulla was horizontal. The medullary surface was covered with warm Ringer solution. The rostral edge of the area postrema in the midline (obex) served as the stereotaxic zero for the rostro-caudal and medio-lateral coordinates. Scopolamine methylbromide (Sigma, 50 p~g/kg initially with supplemental doses 25 t~g/kg) was administered intravenously every 15 min to block cardiac vagal effects. Intramedullary stereotaxic injections were made through a glass micropipette with bevelled tip (O.D. 20-30 /xm) and long shank. Pharmacological agents were dissolved in Ringer. The volume of each injection (100 nl) was monitored by observing movement of the meniscus in the pipette in response to pressure transmitted from a hand-held syringe. The CVLM injection site was 1 mm caudal to the obex, 3 mm lateral from the midline and 3 mm below the dorsal surface of the medulla. Unilateral injections of L-glutamate (Sigma, 10, 100 pmol, 1, 10, 100 nmol) were made in increasing dose order. In different animals, bilateral injections of GABA (Sigma, 1, 5, 25, 125 nmol) were made, also in increasing dose order. Time between injections was at least 5 min for ~.-glutamate and at least 15 min for GABA. After a dose-response curve to injections of L-glutamate (n = 7 rabbits) or GABA (n = 4 rabbits) was established, the area postrema and the nTS were lesioned using a small-ball type electric cautery. Lesions extended rostrally from the level of nucleus commissuralis, along the edge of fourth ventricle, to the caudal ports. In a separate series of rabbits (n = 5) L-glutamate was injected into
99
the CVLM, the nTS and the area postrema were then inhibited using injections of muscimol (Sigma, 1 nmol in 100 nl of Ringer) at 3 rostrocaudal levels. The first site was 1 mm rostral to the obex, at the lateral edge of fourth ventricle, and 0.5 mm below the dorsal surface of the medulla. The second site was at the lateral edge of the area postrema, at the obex level and 0.5 mm below the dorsal surface of the medulla. The third site was at the level of the nucleus commissuralis, in the midline, 0.3 mm below the dorsal surface of the medulla. An additional injection was made into the area postrema. In three different rabbits dose-response curves to unilateral CVLM injections of L-glutamate or bilateral injections of GABA (doses as above) were established after baroreceptor denervation (bilateral sectioning of the carotid sinus, aortic and vagus nerves). The effectivness of the nTS inactivating procedures, and the baroreceptor denervation was checked by noting that the fall in HR observed after intravenous injection of noradrenaline bitartrate (8 ~ g / k g , Sigma) was markedly reduced or abolished. Horseradish peroxidase (final concentration 1%) was added to the injectate before injections into the CVLM a n d / o r the nTS. After the experiment, the animal was killed with an overdose of pentobarbitone sodium (100 m g/ kg i.v.) and perfused via the heart with buffered formaldehyde/ glutaraldehyde. Transverse sections (50/zm) were made of the medulla and horseradish peroxidase was detected by the diaminobenzidine reaction. Baseline values of AP, HR, and changes of these values were recorded. Data were expressed as mean + S.E.M. Changes in values were compared using linear regression, analysis of variance with repeated measures a n d / o r paired t-test.
Results
Histological verification of microinjection sites within the CVLM showed that injections were centered 1 mm caudal to the obex, between the nucleus ambiguus and the lateral reticular nucleus, where the depressor neurons are located
[18]. The injections of muscimol were within the confines of the nTS, the dorsal motor nucleus of the vagus and the area postrema. The HRP staining spread along the rostrocaudal extent of the nTS, from the commisural nucleus to the pontine portion of the nTS. The nTS lesions extended
Fig. 1. Photomicrographs (left half of each section) and diagrams (right half of each section) of Nissl-stained transverse sections of 3 rostro-caudal levels of medulla (distance from obex on left side) showing the location of lesions of the nTS. Gray shadow area indicates injection site. Abbreviations: IO, inferior olive; LRN, lateral reticular nucleus; MVN, medial vestibular nucleus; nA, nucleus ambiguus; nPH, nucleus prepositus hypoglossi; nTS, nucleus tractus solitarius; py, pyramidal tract; Vsp, spinal nucleus of the trigeminal nerve; XII, hypoglossal nucleus.
100
0"
0.01
Dose of L-glutamate (nmols) 0.1 1 10
100
~5
-10v
-20-
-301 ~ -40~ -50 •" -60
r = 0.88 P 0.05, Fig. 2). Similarly the linear regression between dose of L-glutamate and fall in AP, expressed as percentage changes from baseline, was significant before and after injection of muscimol into the nTS ( P < 0.01) but slopes of the regression lines were not different ( P > 0.05). Similar results were obtained when t.-glutamate was injected into the CVLM before and after cauterization of the nTS. Significant ( P < 0.01) linear regressions between log dose of l.glutamate and fall in AP were observed in both situations but the pre-lesion slope (7.4 mmHg per log dose of L-glutamate) was not significantly ( P > 0.05) different from the post-lesion slope (10.9 mmHg per log dose of L-glutamate), although, as can be seen in Fig. 3, there was a tendency for the responses to be greater after the lesions. Indeed t-tests showed that the falls in AP with 10 and 100 nmol of L-glutamate were significantly higher after the lesions (P < 0.01). Bilateral injection of GABA into the CVLM in animals with intact nTS caused a dose-related increase in AP ( P < 0.01, n = 24 injections in four animals). The slope of the regression line was 4.5 mmHg per log dose of GABA. After nTS
0
Dose of L-glutamate (nmols) 0.1 I 10
0.01
100
-10 .~ -20 m ~a
-30
~ -40
......o
before'e
r = 0.88 P
.......
.........................
~
.~ -50 e,
-60
P < 0.01
-7C Fig. 3. Relationship between the amount of L-glutamate unilaterally injected into the caudal ventrolateral medulla and fall in arterial pressure before and after lesions of the nTS. Linear regression is significant (P 0.05).
101
lesions the corresponding slope was significantly increased (17.3 mmHg per log dose, P < 0.01), as shown in Figs. 4 and 5. The slope of the regression line between dose of GABA and the pressor response expressed as a percentage of the baseline was also significantly greater after the lesions of the nTS (P < 0.01). After baroreceptor denervation the slope of the regression line linking fall in AP to log dose of L-glutamate injected into the CVLM was 6.9 mmHg per log dose of L-glutamate (P < 0.01, n = 20 injections in three animals). This value was unchanged from the slope recorded in non-denervated animals (P > 0.05). The corresponding slope linking a rise in AP to CVLM injection of GABA was 19.2 mmHg per log dose (P < 0.01, n = 16 injections in three animals) and this value
A
was significantly greater (P < 0.01) than the slope of the control regression line.
Discussion The arterial pressure responses evoked by chemical stimulation or inhibition of the CVLM were still present after pharmacological blockade or lesioning of the nTS. The slope of the dose-response curves for L-glutamate and GABA were not reduced by either the nTS lesions or the muscimol injections. The results therefore demonstrate that the cardiovascular effects of alteration of neuronal function in the CVLM are not directly dependent on the integrity of the nTS. Our findings are in keeping with the view
1S01
I'11ASIC ARTERIAL PRESSURE 100 J (ramHg) 50
125sl
MEAN 1501 ARTERIAL PRESSURE100 1 (mmHg) 50 -J
B
15o1
PHASIC ARTERIAL PRESSURE 100 1 (mmHg) 50 J MEAN 150] ARTERIAL PRESSURE100 1 (mmHg) 50 J 1nmol
5 nn'~ol
25nmol
125nmol
Fig. 4. Polygraph records of arterial pressure showing effect of bilateral injections of different amounts of GABA into the caudal ventrolateral medulla before (A) and after (B) lesions of the nTS.
102
~ +90
~ +~o fi
+70 +6O +50 +40.
after lesions r = 0.87 P
