Baroreceptor influence on a spinal cardiovascular reflex1 FRANCO LIOYAND PETERM. SZETO
Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by San Diego (UCSD) on 01/11/15 For personal use only.
Dcpsmrtrnent of Yiiysiology, University of British Colunzbin, Yatzcouver, B.C. Canada V6T 1W5 Received June 14, 1978 EIOY, F., and SZETO, P. M. 1979. Baroreceptor influence on a spinal cardiovascular reflex. Can. J. Physiol. Pharmacol. 57, 147-1 5 1. A stretch of the walls of the thoracic aorta, performed in vagotomized cats without obstructing aortic flow, induces increases in heart rate, myocardial contractility, anci arterial pressure. These reflex responses are still present after high spinal section. Cats under chloralose-urethane anesthesia were vagotomized and one carotid sinus was isolated and perfused with arterial blood at constant flow. The contralateral carotid sinus nerve and both aortic nerves were sectioned. A stretch of the walls of the thoracic aorta between the 7th and 10th intercostal arteries induced a reflex increase in mean arterial pressure of 29 i:2 mmHg (mean i:SE). Stepwise increases of carotid sinus pressure (CSY) or electrical stimulation of the carotid sinus nerve induced stepwise decreases of this reflex response. At m'aximal baroreceptor stimulation (CSP 212 t 9 mmHg) the reflex response to aortic stretch was reduced by 42%. These experiments show that this spinal cardiovascular reflex is at least partially under the inhibitory control of the baroreceptor input.
LIQY, F., et SZETO, P. M. 1979. Baroreceptor influence on a spinal cardiovascular reflex. Can. J . Physiol. Pharmacol. 57, 147-151. L'ktirement des parois de l'aorte thoracique pratique sur des chats vagotomisks sans obstruction du dkbit aortique, produit une augmentation du rythme cardiaque, de la comtractilitk du myocai-cle ainsi que de la pression artkrielle. Ces rCponses rtflexes existent encore aprks section spinale haute. Les chats, anesthksits au chlordose-urkthane. soilt vagotomisks; un sinus carotidien est isolk et perfus6 avec du sang lrrtCriel 2 dkbit constant. Le nerf du sinus carotidien contra-latCral et les deux nerfs aortiques sont sectionnds. E'ktirement des parois de l'aorte thoracique entre les 72me et 10Pme artkres intercostales induit une augmentation rCflexe de la pression artkrielle moyenne de 29 2 2 mmHg (moyenne z! SE!. Des augmentations par palier de la pression du sinus carotidien (CSP) ou une stimulation klectrique du nerf du sinus carotidien induisent des diminutions par palier de cette rkponse rkflexe. La rkponse rCflexe B l'ktirement aortique est rkduite de 42% pour une stimulation maximale des barorkcepteurs (CSP 212 zk 9 mmHg) . Ces expiriences montrent que ce rkflexe cardiovasculaire spinal est, au moins partiellement. sous le contrale inhibiteur des baroricepteurs d'entrke. [Traduit par le journal]
Introduction It has been shown that hemodynamic or chemical stimuli elicit reflex cardiovascular responses in vagotomized spinal animals (Brown and Malliani 197 1; Malliani et al. 1971). Similar responses can also be induced by electrical stimulation of visceral afferent fibres reaching the spinal cord within the sympathetic nerves (Malliani et al. 1973; Peterson and Brown 1 97 1) . The interactions between these spinal cardiovascular reflexes and the better known supraspinal regulator mechanisms are not well understood. Somatosympathetic reflexes appear to be under baroreceptor inhibitory control (Sato and Schmidt 1973), A e s n ~ v l n ~ o CSN, ~ s : carotid sinus nerve(s): AS, aortic stretch; CSP, carotid perfusion pressure, FAP, femoral artery pressure. 'Supported by a Grant of the British Columbia Heart Foundation.
which is at least partially effective also on their "early spinal component" (Coote and McLeod 1974). In previous experiments we have demonstrated that a stretch of the walls of the thoracic aorta, performed in vagotomized cats with or without spinal section, elicits reflex hernodynamic responses which can be attributed to an increase of sympathetic activity inducing vasoconstriction of the external iliac, superior mesenteric, and renal beds (Szeto aind Lioy 1978) and affecting also the heart and probably the adrenal medulla (Lioy et al. 1974). The present experiments were designed to investigate the interactions between this s ~ i n a lcardiovascular reflex (the AS response) and ihebaroreceptor reflex. ~ethods Cats were anesthetized with a mixture of urethane (250
0008-4212/79/020147-05!$01.00/0 @ 1979 National Research Council of Canada/Conseil national de recherehes du Canada
Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by San Diego (UCSD) on 01/11/15 For personal use only.
148
CAN. J. PHYSIBL. PHARMACBL. VOL. 57, 1979
mgikg) and alpha-ch%oralose(60 mg/kg, ip). The cervical vagosympathetic trunks and aortic nerves were cut and u carotid and a femoral artery were canilulated with short, wide-bore catheters. The animals were paralyzed with gallamine triethiodide (Flaxedil, Poulenc, Montreal; 2.5 mgikg) and ventilated with a mixture of 50% 0- in N2 by means of a Harvard respirator (model 614) connected to a tracheal cannula. Ventilatory rate was adjusted to maintain arterial gases and pH within physiological limits (P,,, I35 t I 5 mmHg; qco,, 28 k 4 mmHg, pH 7.4 9 0.05). These PC,, and pH values are normal for lightly anesthetized, spontaneously breathing cats, according to observations made in our laboratory (unpublished) and in others was continuously msn(Miserocchi 1976). End-tidal Y itored by means of a Beckman LB-I infrared analyzer and blood gases and pH were measured every 30 min with an Instrumentation Laboratories gas analyzer (model 111 3). The blood withdrawn for gas analysis (0.5 mL) was replaced with Dextran 75. Appropriate doses of sodium bicarbonate ( I mequiv.imL) were administered intravenously when necessary. The guidelines of the American Physiological Society regarding anesthetized, curarized aninlals were observed.
,,,
Tlroracic Aorta Cannulation All aninlals were placed on their right side and the left hemithorax was widely opened from the 4th to the 10th rib. A special cannula was used to stretch the walls of the aorta without obstructiilg blood flow. It consisted of a stainless steel tube surrounded by a thin rubber cylinder which could be inflated via another small metal tube mounted perpendicularly close to the end of the cannula. The animal was heparinized ( 3 mg/kg) and, after clamping the aorta caudal to the left subclavian artery, the vessel was completely divided and the cannula inserted. Cannulas of different size (5-7 cm long, 3-5 mrn inside diameter) were selected according to the size of the animal so that they fitted snugly into the vessel. The two cut ends of the aorta were ligated around the lower end of the cannula with the side tube passing out between them. The cannulation procedure took between 11 and 1.5 min. When the balloon was inflated with 0.4-0.9 m% of saline solution, the aortic walls were stretched between the 7th and 10th intercostal arteries. C S N Sfinartlarion The CSN were carefully isolated under a dissection microscope and prepared for section and stimulation. Barsreceptor fibres in the GSN were stimulated with square pulses from an S8 Grass stimulator. The parameters chosen for stimlalation of the CSN ( 1.5-3 V; 3 ms; 5-15 Hz) were based on a study by Neil ct a?. (1949). These authors found that ill the cat under chloralose anesthesia, long-duration pulses activate mainly baroreceptor fibres while chemoreceptor fibres are selectively activated by pulses of shorter dlaration (0.07 ms). In 18 cats one carotid sinus was isolated by ligating all vessels with the exception of the common and external carotid and the occipital arteries. Blood was withdrawn from the centrally cannulated common carotid artery and pumped at constant flow through a heated (37°C) water jacket back into the same artery by means of a peristaltic pump (Narvmrd Apparatus, model 11210). The blood left the sinus via, the cannulated external carotid artery and flowed into the jugular vein. Perfusion pressure in the sinus, measured on the inflow line, could be changed by means of a screw clamp on the outflow line.
Arterial pressures were measured with Statham P23Db strain gauges. The catheter mailometer systen~shad a flat (5%) frequency response to 30 Hz, as calculated by their response to step increases in pressure (Fry 1960). The signals were fed to a transducericonverter (S.E. Laboratories, Feltham England, type SE 905 ), and recorded on a direct print UV recorder (S.E. Laboratories, type SE 3006). Data were collected only from animals that had a mean femoral artery pressure above 100 mmHg. The parameters measured in each animal in each experimental situation were averaged and these average values were used to calculate the means and standard errors presented in the text,
Results Fifteen vagotomized and aortic denervated cats were placed in three groups of five animaHs each. In group 1 both CSN were cut and one of them was stimulated electrically. In the other animals one carotid sinus was perfused with arterial blood froin the same animal and the contralateral CSN was cut (group 2 ) or the contralateral carotid artery was occluded (group 3 ) . Arterial pressure was lower in group 3 than in group 1 and group 2 (Table 1 ). When AS was performed, arterial pressure increased significantly in all three groups. The magnitude of this reflex response (the AS response) was somewhat smaller in group 3 than in the other two groups. Baroreceptor Stimulation Electrical stimulation of the central end sf one CSN (group 1 ) or increases in CSP in groups 2 and 3 induced a significant ( P < 0.005) fall in carotid systolic and diastolic pressures and in mean FAP, characteristic of the baroreceptor reflex (Fig. 1, Table 1). Iia most cases arterial pressures remained steady at the new lower level throughout the period of baroreceptor stimulation. In those cases in which arterial pressure 'escaped' back toward the prestiinulation 'levels, the shift in base line was taken into account in determining the magnitude of the AS response. When AS was performed during baroreceptor stimulation the reflex response was significantly reduced (Table 1) . Figure 1 shows the progressive suppression of the AS response when CSP was increased in steps from 100 to 200 mn~Hg.The degree of suppression of the AS response was related to the frequency of stimulation applied to the CSN or to the level of CSP. This is shown in Fig. 2 where the extent of the reflex response, expressed as a percentage of that obtained in the control situation, is plotted against these two parameters. The effects of CSN stimulation both on arterial pressure and on the AS response were maximal at frequencies of 10-1 5 Hz.
LIOY AND SZETO
TABLE 1. Effect s f baroreceptor stimulation on the arterial pressure and the reflex respomse induced by aortic stretch in vagotomized cats N
No. trials
CSN stimulation (both CSN cut)
5
37
CS perfusion (other CSN cut)
5
33
CS perfusion (other carotid occluded)
5
32
Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by San Diego (UCSD) on 01/11/15 For personal use only.
Group
Mean FAP
AAS
1 Control Stimulation (1 5 Hz) B
2
3
Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by San Diego (UCSD) on 01/11/15 For personal use only.
Dcpsmrtrnent of Yiiysiology, University of British Colunzbin, Yatzcouver, B.C. Canada V6T 1W5 Received June 14, 1978 EIOY, F., and SZETO, P. M. 1979. Baroreceptor influence on a spinal cardiovascular reflex. Can. J. Physiol. Pharmacol. 57, 147-1 5 1. A stretch of the walls of the thoracic aorta, performed in vagotomized cats without obstructing aortic flow, induces increases in heart rate, myocardial contractility, anci arterial pressure. These reflex responses are still present after high spinal section. Cats under chloralose-urethane anesthesia were vagotomized and one carotid sinus was isolated and perfused with arterial blood at constant flow. The contralateral carotid sinus nerve and both aortic nerves were sectioned. A stretch of the walls of the thoracic aorta between the 7th and 10th intercostal arteries induced a reflex increase in mean arterial pressure of 29 i:2 mmHg (mean i:SE). Stepwise increases of carotid sinus pressure (CSY) or electrical stimulation of the carotid sinus nerve induced stepwise decreases of this reflex response. At m'aximal baroreceptor stimulation (CSP 212 t 9 mmHg) the reflex response to aortic stretch was reduced by 42%. These experiments show that this spinal cardiovascular reflex is at least partially under the inhibitory control of the baroreceptor input.
LIQY, F., et SZETO, P. M. 1979. Baroreceptor influence on a spinal cardiovascular reflex. Can. J . Physiol. Pharmacol. 57, 147-151. L'ktirement des parois de l'aorte thoracique pratique sur des chats vagotomisks sans obstruction du dkbit aortique, produit une augmentation du rythme cardiaque, de la comtractilitk du myocai-cle ainsi que de la pression artkrielle. Ces rCponses rtflexes existent encore aprks section spinale haute. Les chats, anesthksits au chlordose-urkthane. soilt vagotomisks; un sinus carotidien est isolk et perfus6 avec du sang lrrtCriel 2 dkbit constant. Le nerf du sinus carotidien contra-latCral et les deux nerfs aortiques sont sectionnds. E'ktirement des parois de l'aorte thoracique entre les 72me et 10Pme artkres intercostales induit une augmentation rCflexe de la pression artkrielle moyenne de 29 2 2 mmHg (moyenne z! SE!. Des augmentations par palier de la pression du sinus carotidien (CSP) ou une stimulation klectrique du nerf du sinus carotidien induisent des diminutions par palier de cette rkponse rkflexe. La rkponse rCflexe B l'ktirement aortique est rkduite de 42% pour une stimulation maximale des barorkcepteurs (CSP 212 zk 9 mmHg) . Ces expiriences montrent que ce rkflexe cardiovasculaire spinal est, au moins partiellement. sous le contrale inhibiteur des baroricepteurs d'entrke. [Traduit par le journal]
Introduction It has been shown that hemodynamic or chemical stimuli elicit reflex cardiovascular responses in vagotomized spinal animals (Brown and Malliani 197 1; Malliani et al. 1971). Similar responses can also be induced by electrical stimulation of visceral afferent fibres reaching the spinal cord within the sympathetic nerves (Malliani et al. 1973; Peterson and Brown 1 97 1) . The interactions between these spinal cardiovascular reflexes and the better known supraspinal regulator mechanisms are not well understood. Somatosympathetic reflexes appear to be under baroreceptor inhibitory control (Sato and Schmidt 1973), A e s n ~ v l n ~ o CSN, ~ s : carotid sinus nerve(s): AS, aortic stretch; CSP, carotid perfusion pressure, FAP, femoral artery pressure. 'Supported by a Grant of the British Columbia Heart Foundation.
which is at least partially effective also on their "early spinal component" (Coote and McLeod 1974). In previous experiments we have demonstrated that a stretch of the walls of the thoracic aorta, performed in vagotomized cats with or without spinal section, elicits reflex hernodynamic responses which can be attributed to an increase of sympathetic activity inducing vasoconstriction of the external iliac, superior mesenteric, and renal beds (Szeto aind Lioy 1978) and affecting also the heart and probably the adrenal medulla (Lioy et al. 1974). The present experiments were designed to investigate the interactions between this s ~ i n a lcardiovascular reflex (the AS response) and ihebaroreceptor reflex. ~ethods Cats were anesthetized with a mixture of urethane (250
0008-4212/79/020147-05!$01.00/0 @ 1979 National Research Council of Canada/Conseil national de recherehes du Canada
Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by San Diego (UCSD) on 01/11/15 For personal use only.
148
CAN. J. PHYSIBL. PHARMACBL. VOL. 57, 1979
mgikg) and alpha-ch%oralose(60 mg/kg, ip). The cervical vagosympathetic trunks and aortic nerves were cut and u carotid and a femoral artery were canilulated with short, wide-bore catheters. The animals were paralyzed with gallamine triethiodide (Flaxedil, Poulenc, Montreal; 2.5 mgikg) and ventilated with a mixture of 50% 0- in N2 by means of a Harvard respirator (model 614) connected to a tracheal cannula. Ventilatory rate was adjusted to maintain arterial gases and pH within physiological limits (P,,, I35 t I 5 mmHg; qco,, 28 k 4 mmHg, pH 7.4 9 0.05). These PC,, and pH values are normal for lightly anesthetized, spontaneously breathing cats, according to observations made in our laboratory (unpublished) and in others was continuously msn(Miserocchi 1976). End-tidal Y itored by means of a Beckman LB-I infrared analyzer and blood gases and pH were measured every 30 min with an Instrumentation Laboratories gas analyzer (model 111 3). The blood withdrawn for gas analysis (0.5 mL) was replaced with Dextran 75. Appropriate doses of sodium bicarbonate ( I mequiv.imL) were administered intravenously when necessary. The guidelines of the American Physiological Society regarding anesthetized, curarized aninlals were observed.
,,,
Tlroracic Aorta Cannulation All aninlals were placed on their right side and the left hemithorax was widely opened from the 4th to the 10th rib. A special cannula was used to stretch the walls of the aorta without obstructiilg blood flow. It consisted of a stainless steel tube surrounded by a thin rubber cylinder which could be inflated via another small metal tube mounted perpendicularly close to the end of the cannula. The animal was heparinized ( 3 mg/kg) and, after clamping the aorta caudal to the left subclavian artery, the vessel was completely divided and the cannula inserted. Cannulas of different size (5-7 cm long, 3-5 mrn inside diameter) were selected according to the size of the animal so that they fitted snugly into the vessel. The two cut ends of the aorta were ligated around the lower end of the cannula with the side tube passing out between them. The cannulation procedure took between 11 and 1.5 min. When the balloon was inflated with 0.4-0.9 m% of saline solution, the aortic walls were stretched between the 7th and 10th intercostal arteries. C S N Sfinartlarion The CSN were carefully isolated under a dissection microscope and prepared for section and stimulation. Barsreceptor fibres in the GSN were stimulated with square pulses from an S8 Grass stimulator. The parameters chosen for stimlalation of the CSN ( 1.5-3 V; 3 ms; 5-15 Hz) were based on a study by Neil ct a?. (1949). These authors found that ill the cat under chloralose anesthesia, long-duration pulses activate mainly baroreceptor fibres while chemoreceptor fibres are selectively activated by pulses of shorter dlaration (0.07 ms). In 18 cats one carotid sinus was isolated by ligating all vessels with the exception of the common and external carotid and the occipital arteries. Blood was withdrawn from the centrally cannulated common carotid artery and pumped at constant flow through a heated (37°C) water jacket back into the same artery by means of a peristaltic pump (Narvmrd Apparatus, model 11210). The blood left the sinus via, the cannulated external carotid artery and flowed into the jugular vein. Perfusion pressure in the sinus, measured on the inflow line, could be changed by means of a screw clamp on the outflow line.
Arterial pressures were measured with Statham P23Db strain gauges. The catheter mailometer systen~shad a flat (5%) frequency response to 30 Hz, as calculated by their response to step increases in pressure (Fry 1960). The signals were fed to a transducericonverter (S.E. Laboratories, Feltham England, type SE 905 ), and recorded on a direct print UV recorder (S.E. Laboratories, type SE 3006). Data were collected only from animals that had a mean femoral artery pressure above 100 mmHg. The parameters measured in each animal in each experimental situation were averaged and these average values were used to calculate the means and standard errors presented in the text,
Results Fifteen vagotomized and aortic denervated cats were placed in three groups of five animaHs each. In group 1 both CSN were cut and one of them was stimulated electrically. In the other animals one carotid sinus was perfused with arterial blood froin the same animal and the contralateral CSN was cut (group 2 ) or the contralateral carotid artery was occluded (group 3 ) . Arterial pressure was lower in group 3 than in group 1 and group 2 (Table 1 ). When AS was performed, arterial pressure increased significantly in all three groups. The magnitude of this reflex response (the AS response) was somewhat smaller in group 3 than in the other two groups. Baroreceptor Stimulation Electrical stimulation of the central end sf one CSN (group 1 ) or increases in CSP in groups 2 and 3 induced a significant ( P < 0.005) fall in carotid systolic and diastolic pressures and in mean FAP, characteristic of the baroreceptor reflex (Fig. 1, Table 1). Iia most cases arterial pressures remained steady at the new lower level throughout the period of baroreceptor stimulation. In those cases in which arterial pressure 'escaped' back toward the prestiinulation 'levels, the shift in base line was taken into account in determining the magnitude of the AS response. When AS was performed during baroreceptor stimulation the reflex response was significantly reduced (Table 1) . Figure 1 shows the progressive suppression of the AS response when CSP was increased in steps from 100 to 200 mn~Hg.The degree of suppression of the AS response was related to the frequency of stimulation applied to the CSN or to the level of CSP. This is shown in Fig. 2 where the extent of the reflex response, expressed as a percentage of that obtained in the control situation, is plotted against these two parameters. The effects of CSN stimulation both on arterial pressure and on the AS response were maximal at frequencies of 10-1 5 Hz.
LIOY AND SZETO
TABLE 1. Effect s f baroreceptor stimulation on the arterial pressure and the reflex respomse induced by aortic stretch in vagotomized cats N
No. trials
CSN stimulation (both CSN cut)
5
37
CS perfusion (other CSN cut)
5
33
CS perfusion (other carotid occluded)
5
32
Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by San Diego (UCSD) on 01/11/15 For personal use only.
Group
Mean FAP
AAS
1 Control Stimulation (1 5 Hz) B
2
3
