Carotid Sinus Hypotension Research Articles

Preferential baroreflex control of left ventricular diastolic function at rest and during mild dynamic exercise.

Carotid sinus hypotension elicits large baroreflex‐induced increases in peripheral resistance but has relatively little effect on left ventricular systolic function. However, baroreflex control over left ventricular relaxation is unknown and diastolic function can contribute importantly to overall cardiac performance, especially during periods of stress such as dynamic exercise. Therefore, we investigated the relative effects of bilateral carotid occlusion (BCO) on left ventricular systolic and diastolic function (±dP/dtmax/min) in conscious dogs at rest and during exercise (3.2 km/h). As expected, exercise caused a significant increase in heart rate (HR), +dP/dtmax, stroke volume (SV), and therefore cardiac output (CO) but also in total vascular conductance (TVC) and as a result arterial pressure (AP) remained unchanged. No significant change occurred in ‐dP/dtmin, thus ±dP/dtmax‐min ratio substantially increased. At rest and during mild dynamic exercise, BCO caused no significant change in CO and therefore the rise in AP was due to a significant decrease in TVC. BCO increased ‐dP/dtmin, with no change in +dP/dtmax, therefore ±dP/dtmax‐min ratio significantly decreased. We conclude that the increase in sympathetic activity to the heart elicited by carotid baroreceptor unloading preferentially improves left ventricular diastolic function. Supported by HL‐55473.

Induction of paradoxic bradycardia in rats by inferior vena cava occlusion during the administration of isoproterenol: the essential role of augmented sympathetic tone.

Testing human susceptibility for vasodepressor reactions involves combining venous return restriction by passive upright tilting and administering isoproterenol. While sympathetic tone is usually increased by the stimuli that incite a vasodepressor reaction, it is not known if the increased sympathetic tone is an essential or passive component of the mechanism that triggers the reaction. Given that paradoxic bradycardia is a major manifestation of vasodepressor reactions and allowing for the possible extrapolation between paradoxic bradycardia in rats and vasodepressor reactions, we examined the role of sympathetic tone in the paradoxic bradycardia reaction. Paradoxic bradycardia was induced in rats by inferior vena cava occlusion during an isoproterenol infusion. To examine the role of increased sympathetic tone on this reaction, we studied whether carotid artery perfusion (80 to 100 mmHg) during inferior vena cava occlusion, a maneuver that blunts the rise in sympathetic tone, inhibits paradoxic bradycardia. The maximum changes in R-R were measured during 60 seconds of inferior vena cava occlusion as follows: (a) in control the heart rate accelerated (delta R-R - 10.2 +/- 2.3 msec, P < 0.001); (b) during an infusion of isoproterenol, paradoxic bradycardia occurred (delta R-R + 140.6 +/- 18.2 msec, P < 0.001), and this was inhibited by common carotid artery perfusion (delta R-R - 6.6 +/- 1.5 msec, P < 0.001); and (c) following carotid sinus denervation and during an infusion of isoproterenol, paradoxic bradycardia was induced without and with carotid artery perfusion (delta R-R + 122.6 +/- 12.0 msec, P < 0.001; delta R-R + 151.8 +/- 12.7 msec, P < 0.001, respectively). Since carotid artery perfusion during inferior vena cava occlusion inhibits paradoxic bradycardia only when the carotid sinus is innervated, we conclude that carotid artery perfusion blocks the reaction by increasing carotid sinus afferents, thereby limiting the increased sympathetic tone during inferior vena cava occlusion, and not as a result of cerebral perfusion. Thus, the paradoxic bradycardia resulting from inferior vena cava occlusion requires activation of sympathetic tone as a result of carotid sinus hypotension.

Effects of neuropeptide‐Y on renal function and its interaction with sympathetic stimulation in conscious dogs.

1. The effects of neuropeptide-Y (NPY) on renal function were investigated in conscious foxhounds. 2. Dose-response curves (n = 7) were obtained for NPY by measuring renal blood flow (RBF), glomerular filtration rate (GFR), urine excretion (VU), sodium excretion (VNa), potassium excretion (VK) and plasma renin activity (PRA) at different infusion rates. All variables decreased with increasing infusion rates except for PRA, which surprisingly did not change during the different infusion rates. 3. The influence of the non-constrictor dose of NPY at control pressure, and after servo-controlling renal arterial pressure at 80 mmHg, was determined for these parameters (n = 6). 4. This was repeated during a reflex sympathetic activation via carotid sinus hypotension, in order to quantify a possible interaction between the sympathetic transmitter and co-transmitter (n = 6). 5. The subthreshold NPY dose raised plasma NPY-like immunoreactivity (NPY-LI IR) significantly (renal venous plasma: 54 +/- 13 vs. 405 +/- 117 pg ml-1; P less than 0.05) and enhanced the pressure-dependent (80 mmHg) antidiuresis (0.48 +/- 0.06 vs. 0.24 +/- 0.02 ml min-1; P less than 0.05), antinatriuresis (46 +/- 11 vs. 25 +/- 3 mumol min-1; P less than 0.05), antikaliuresis (19 +/- 4 vs. 9 +/- 0.7 mumol min-1; P less than 0.05) and pressure-dependent renin release (0.95 +/- 0.27 vs. 3.0 +/- 1.1 ng angiotensin I ml-1 h-1; P less than 0.05). These effects are consistent with a non-uniform vasoconstrictor action of NPY in the renal vascular bed (see accompanying papers). 6. The effects of NPY plus sympathetic activation were less than the sum of the two individual effects, which may rely on a presynaptic mechanism.

Cardiopulmonary receptors and coronary circulation

Coronary blood flow has long been regarded as being regulated primarily by the metabolic demand of the myocardium [1,2]. Experimental and clinical reports [3-9], however, indicate that such coronary regulation can be overridden by the adrenergic drive to the heart. In particular, previous studies in dogs [7,10] demonstrated that carotid sinus hypotension results in a reflex sympathetic a-receptor coronary vasoconstriction, independent of changes in myocardial oxygen metabolism or aortic pressure. Other investigators [4] observed in dogs that stimulation of the carotid sinus nerve can produce a profound coronary vasodilatation mediated by reflex suppression of tonic a-vasoconstrictor tone. Finally, we described in humans a reflex increase of coronary vascular resistance induced by reduction in carotid transmural pressure [11]. While a modulatory role of arterial baroreceptors has been demonstrated, the possible influence exerted by cardiopulmonary receptors on the coronary vascular tone is still debated. It is well known that these receptors affect peripheral vascular tone [12,13]; in addition, Thames [14] has shown reflex withdrawal of renal sympathetic dis-

Baroreflex modulation by cardiopulmonary receptors during chronic sodium depletion.

Chronic sodium to depletion is associated with a reduced baroreflex responsiveness to carotid sinus hypotension. One hypothesis to explain the mechanism of the reduced baroreflex responsiveness involves a redistribution of blood volume toward the cardiopulmonary circulation during sodium depletion. This volume redistribution may result in enhanced discharge of cardiopulmonary volume-sensing mechanoreceptors, which tonically inhibit the expression of the carotid baroreflex. In this study, when the pressor and tachycardic responses to carotid occlusion were tested, the baroreflex responses were significantly smaller in sodium-depleted dogs (P less than 0.05). When the vagal and aortic depressor nerves were removed, the baroreflex responses to carotid occlusion were increased in both sodium-replete and sodium-depleted animals. However, the pressor and tachycardic responses were still attenuated in the sodium-depleted animals after vagotomy (P less than 0.05). Thus the results of this study indicate that cardiopulmonary volume receptor discharge is not increased in the sodium-depleted state, and removal of cardiopulmonary vagal afferent influences does not normalize the impaired baroreflex responsiveness of sodium-depleted animals.

The effect of plasma volume expansion on the response to carotid occlusion in the non-human primate

The purpose of this study was to investigate the effects of plasma volume expansion on the cardiac and peripheral components of the baroreceptor reflex. Nine male Rhesus monkeys were chronically instrumented to measure arterial pressure and aortic blood flow. The aortic arch was denervated at the time of surgery. Bilateral carotid artery occlusion (BCO) was used to elicit the carotid sinus reflex both before and after 25% plasma volume expansion with an iso-osmotic dextran solution. The BCO elicited significant increases in heart rate (HR, 29.8 ± 5.3 bpm) mean arterial pressure (MAP, 55.0 ± 8.2 mm Hg) and total peripheral resistance (TPR, 0.076 ± 0.01 mm Hg/ml/min) coupled with a significant reduction in mean aortic flow (AF, −246.9 ± 55.3 ml/min) and stroke volume (SV, −2.86 ± 0.36 ml). Volume expansion significantly attenuated the HR (15.2 ± 5.8 bpm), MAP (30.4 ± 4.4 mm Hg) and TPR (0.036 ± 0.006 mm Hg/ml/min) response to carotid sinus hypotension. The changes in mean AF and SV elicited by BCO, however, were not significantly different between the control and volume expansion conditions. These data suggest that plasma volume expansion significantly attenuates the baroreceptor reflex control of circulation with a similar reduction in both the peripheral resistance and heart rate components of the response.

Release of norepinephrine from sympathetic nerve efferents by bilateral carotid occlusion.

To investigate the response of the efferent sympathetic nervous system to carotid sinus hypotension, norepinephrine and epinephrine were measured in the dog during control and following bilateral carotid occlusion in arterial, coronary sinus, renal vein, hepatic vein, femoral vein, and pulmonary artery plasma. Mean arterial pressure increased from 109 mmHg during control to 144 and 143 at 1 and 5 min after carotid occlusion, respectively (P less than 0.01). This was associated with an increase in arterial norepinephrine, which could be prevented by the ganglionic blocking agent mecamylamine. While the concentration of norepinephrine rose in all venous effluents, the venous minus arterial norepinephrine difference increased only in the coronary and renal circulations. The results indicate that bilateral carotid occlusion increases the arterial norepinephrine concentration and the overflow of this neurotransmitter from the heart and kidney. The data thus suggest that norepinephrine release from sympathetic axon terminals in the heart and kidney is increased by carotid sinus hypotension. The magnitude of the increase in sympathetic activity evoked by carotid occlusion may have little effect on renal hemodynamics but may have a significant influence on cardiac contractility and coronary blood flow.

Pulmonary vascular response to carotid sinus hypotension in the awake and anaesthetized dog.

The pulmonary haemodynamic response to brachiocephalic artery occlusion (BCO) was studied in nine dogs. The animals were chronically instrumented for the measurement of pulmonary artery pressure and flow together with left atrial pressure. Measurements were performed in the awake state and also at end-tidal halothane levels averaging 0.74 +/- 0.02 (H1), 0.92 +/- 0.02 (H2) and 1.13 +/- 0.03 (H3) %, with and without nitrous oxide. Halothane at any of the above concentrations, with or without nitrous oxide, had no effect on pulmonary vascular resistance compared to awake values. Most importantly, we found no evidence for active pulmonary vasomotion in response to BCO in the awake animal, or at any anaesthetic concentration.

Effect of baroreceptor reflex stimulation on blood flow to an atelectatic lung.

The effect of baroreceptor reflex stimulation by carotid sinus hypotension on the pulmonary vascular response to atelectasis was studied in eight dogs anesthetized with chloralose. Closed-chest dogs with electromagnetic flow probes previously implanted on their left (QL) and main (QT) pulmonary arteries had their left and right lungs ventilated separately. Their carotid sinuses were isolated bilaterally and perfused by a pulsatile pump with a physiological salt solution. After an initial period of bilateral 100% O2 ventilation with carotid sinus perfusion pressures (CSPP) set at each animal's initial mean arterial pressure (98 +/- 19 Torr), the left airway was occluded, QL/QT fell from 0.33 +/- 0.01 to 0.24 +/- 0.02 and PO2 fell from 323 +/- 35 Torr to 74 + 7 Torr. When CSPP was lowered to 21 +/- 3 Torr, there were no changes in QL/QT and PO2. These results suggest that stimulation of the baroreceptor reflex by carotid sinus hypotension does not interfere with the diversion of pulmonary blood flow away from a unilaterally atelectatic lung.

Altered neural control of cardiovascular function in sodium-depleted dogs.

Sodium restriction affects sympathetic control mechanisms by blunting of the reflex pressor response to carotid sinus hypotension, which is reversible by section of vagal afferents. To obtain more direct evidence, sympathetic nerve activity was recorded from a renal nerve (RNA) in 16 normal (NS) and 13 sodium-depleted (SD) dogs anesthetized with morphine-pentobarbital. Integrated RNA was measured during changes in mean arterial pressure (MAP) produced by i.v. infusion of sodium nitroprusside (100 micrograms/kg/min) or phenylephrine (20 micrograms/kg/min). The classical inverse relationship between MAP and integrated RNA was found before and after bilateral vagotomy (VAGT) in both NS and SD dogs. However, RNA in SD dogs, expressed as % of maximal neural firing, was significantly less at any blood pressure level when compared to NS dogs. In addition, the critical pressure (point at which RNA ceased) was reduced in SD vs NS dogs (p less than 0.002). The decreased sympathetic neural firing in SD dogs was abolished after bilateral VAGT, confirming the pronounced buffering effects of vagal afferents on RNA in salt-depleted dogs.

Renin release with carotid occlusion in the conscious dog: role of renal arterial pressure

Page H108: A. P. Rocchini and A. C. Barger. “Renin release with carotid occlusion in the conscious dog: role of renal arterial pressure.” Page H110: the second line of the addendum should read carotid sinus hypotension.

Involvement of renal alpha- and beta-adrenoceptors in release of renin by carotid baroreflex

In anesthetized vagotomized dogs with renal arterial pressure constant, carotid sinus hypotension (BCO) caused a reflex rise in systemic arterial pressure, a fall in renal blood flow, and a similar increase in renin release from both kidneys. Unilateral alpha-adrenoceptor blockade with phenoxybenzamine resulted in an increase in basal renal blood flow, a depression of basal renin release, and an abolition of the responses to BCO in the treated kidney. The untreated kidney responsed to BCO as before. Nonblocked and alpha-blocked kidneys released similar amounts of renin when renal blood flow was mechanically reduced by aortic constriction. Administration of propranolol to the nonblocked kidney prevented the release of renin but not the hemodynamic changes resulting from BCO. The experiments demonstrated that under certain conditions carotid sinus hypotension produced alpha-adrenoceptor-mediated changes in the kidney sufficient to cause increased renin release. A step in the renin release mechanism subsequent to the alpha-adrenoceptor-mediated changes in sensitive to propranolol.

Carotid sinus reflex coronary vasoconstriction during controlled myocardial oxygen metabolism in the dog.

We studied carotid baroreceptor reflex coronary vasoconstriction in closed-chest dogs with controlled aortic blood pressure and myocardial oxygen metabloism. The dogs were anesthetized with morphine and chloralose. Left coronary blood flow was measured by a cannula-tip flowmeter, and myocardial oxygen metabolism was calculated by measuring the arterial-coronary sinus oxygen difference. A bilateral vagotomy was performed in all animals and they were treated with propranolol. Reduction of carotid sinus pressure to 40 mm Hg caused an increase in aortic pressure that was limited to 15 mm Hg by means of a pressure-control reservoir. During carotid hypotension, heart rate and myocardial oxygen metabolism were unchanged but diastolic conronary vascular resistance increased by 21%. Intracoronary artery infusion of norepinephrine had similar effects. After interruption of the reflex are with the alpha-adrenergic receptor antagonist, dibozane, carotid sinus hypotension and the same increase in aortic pressure (15 mm Hg) resulted in only a 5% increase in diastolic coronary resistance. Dibozane also reduced the coronary responses to norepinephrine. It is concluded that carotid sinus hypotension results in reflex sympathetic alpha-receptor coronary vasoconstriction and that this reflex vasoconstriction is independent of changes in myocardial oxygen metabolism or changes in aortic pressure.

Change in liver blood flow and blood content in dogs during direct and reflex alteration of hepatic sympathetic nerve activity.

A mean decrease of 60% in liver blood volume was recorded by a plethysmographic technique during electrical stimulation of the hepatic nerves in anesthetized, vagotomized dogs. A decrease in pressure in the vascularly isolated carotid sinus to 40 mm Hg, from a mean control of 144 mm Hg, decreased liver blood volume by a mean of 16%; arterial blood pressure increased by a mean of 77 mm Hg. Carotid sinus hypotension was accompanied by respective mean increases of 16% and 1.4% in hepatic arterial and portal venous blood flows, and of 45% and 22% in arterial and portal resistances. Increase in sinus pressure to 240 mm Hg increased liver blood volume by a mean of 20%; arterial blood pressure decreased by 90 mm Hg. Sinus hypertension was accompanied by respective mean decreased of 10% and 1.5% in hepatic arterial and portal venous blood flows, and of 44% and 18% in arterial and portal resistances. Interruption of afferent vagal traffic from cardiopulmonary receptors was maximally effective in decreasing liver blood volume at a carotid sinus pressure of 40 mm Hg and was ineffective at carotid sinus pressures greater than 160 mm Hg. Combined withdrawal of carotid and cardiopulmonary vasomotor inhibition decreased liver blood volume by 42%; of this 37% was due to the cardiopulmonary and 63% to the carotid baroreflex. The study showed the canine liver to function as a blood reservoir by active mobilization of a portion of its blood volume.

Combined effect of carotid sinus hypotension and digestion on splanchnic circulation

ARTICLESCombined effect of carotid sinus hypotension and digestion on splanchnic circulationA FronekA FronekPublished Online:01 Dec 1970https://doi.org/10.1152/ajplegacy.1970.219.6.1759MoreSectionsPDF (875 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByAcute effects of alcohol and food intake on cardiac performanceProgress in Cardiovascular Diseases, Vol. 32, No. 5Abdominalorgane More from this issue > Volume 219Issue 6December 1970Pages 1759-1762 Copyright & PermissionsCopyright © 1970 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1970.219.6.1759PubMed5485693History Published online 1 December 1970 Published in print 1 December 1970 Metrics

Carotid sinus reflex control of coronary blood flow.

The role of the carotid sinus reflex in control of the blood flow in the left circumflex coronary artery was studied in nine open-chest dogs anesthetized with chloralose. Flow was measured with an electromagnetic flowmeter. The effects of bilateral common carotid occlusion were examined in a three-part experiment in each dog. (1) Under vagotomy (control) conditions, occlusion of both common carotid arteries resulted in tachycardia, increased blood pressure, and a decrease in coronary artery resistance. (2) After beta-receptor blockade with propranolol, 1.0 mg/kg, carotid sinus hypotension still resulted in increased blood pressure but the tachycardia was blocked, and coronary artery resistance increased. (3) Following rapid cardiac sympathectomy, carotid sinus hypotension still resulted in a reflex rise in systemic blood pressure but coronary resistance remained steady. This demonstrated the reflex nature of the increased coronary resistance observed after beta-receptor blockade. It is concluded that the coronary circulation is under reflex control and that sympathetic coronary artery vasomotion is a part of a carotid sinus reflex.

Sympathetic Vasoconstrictive Responses during Exercise- or Drug-Induced Vasodilatation

The effect of exercise on the vasoconstrictive response to sympathetic stimulation was studied by observing the changes in perfusion pressure in dogs' hindlimbs perfused at constant flow. During steady-state simulated exercise, a time-dependent increase occurred between 10 and 30 minutes in the magnitude of response to lumbar trunk stimulation or carotid sinus hypotension. This was present (although to a reduced Degrees) in drug-induced vasodilatation and in exercising limbs perfused at constant pressure. The time-dependent change was not due to (1) repetition of stimulus, (2) artifact from muscle electrodes, (3) circulating vasoactive substances, (4) skin circulation, or (5) pH, P CO 2 , or temperature of the perfusing blood. When norepinephrine was used as the vasoconstrictive stimulus, no time-dependent change was noted. After stabilization, the frequency-response curve of exercising muscle exceeded that at rest at all blood concentrations of norepinephrine and at all save the lowest frequencies of stimulation. It was concluded that vascular smooth muscle can develop greater tension from greater initial length. However, during exercise some factor which operates between the sympathetic nerve ending and the receptor site on vascular smooth muscle initially tends to depress this enhanced ability to develop tension.

Hemodynamics and alveolar-arterial PO2 differences at varying PaCO2 in anesthetized man.

Hemodynamics and alveolar-arterial PO2 differences at varying PaCO2 in anesthetized man.

Physiological differences between the effects of neuronally released and bloodborne norepinephrine on beta adrenergic receptors in the arterial bed of the dog.

This investigation was designed to define the role of the beta adrenergic receptors in the regulation of peripheral vascular resistance and to determine whether norepinephrine released from nerve terminals acts at the same receptor sites in the arterial bed as injected norepinephrine. In 34 anesthetized dogs the skinned hindlimb was perfused at a constant flow rate, and in 8 dogs a segment of the splanchnic vascular bed was similarly perfused through the aorta. The hemodynamic responses of the isolated perfused beds of control dogs were compared with those of dogs in which the alpha receptors had previously been blocked with phenoxybenzamine, thereby maximizing any contribution of the beta receptors. In the control animals, both carotid sinus hypotension and norepinephrine administered directly into the perfused segment increased vascular resistance. In those animals subjected to alpha-receptor blockade, carotid sinus hypotension still caused reflex vasoconstriction, though it was considerably attenuated, but intra-arterially injected norepinephrine produced vasodilation. Following subsequent beta-receptor blockade, no potentiation of reflex constriction occurred, although the response to injected norepinephrine reverted to constriction. These findings suggest that norepinephrine released from nerve terminals in the arterial tree does not produce physiologically significant beta-receptor stimulation; humorally transported norepinephrine, however, stimulates both alpha and beta receptors.

PERIPHERAL RESISTANCE RESPONSE TO OCCLUSION OF VISCERAL ARTERIES.

AbstractIn order to compare the effect of visceral and carotid sinus hypotension on the resistance vessels the peripheral resistance in 3 areas (hind body, kidneys and head) in the cat has been investigated by means of the constant perfusion rate technique during occlusion and desocclusion of visceral (coeliac, superior mesenteric and renal) arteries and of the carotid arteries. In all 3 areas clamping of the visceral arteries provoked a vasodilatation whereas a vasoconstriction in the hind body and kidney was observed during carotid artery occlusion. The clampings always produced significant rises in the general arterial blood pressure. The pressor response caused by visceral artery occlusion thus is produced in spite of a widespread dilatation of the resistance vessels—not as a consequence of a constriction in the same vessels. Denervation of the carotid sinuses plus section of the vago‐sympathetic trunks nearly always abolished the vasodilatation. Stabilising the blood pressure by means of a compensating device always abolished the vasodilatation during visceral artery occlusion. Under these circumstances the vasodilatation was not replaced by a vasoconstriction in the periphery. It has thus not been possible to demonstrate baroreceptor activity in the visceral arteries even under circumstances where the activity of the sino‐cardio‐aortic baroreceptor reflexes was eliminated.