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Journal ArticleDOI

Reflex Vascular Responses to Stimulation of Chemoreceptors with Nicotine and Cyanide: Activation of Adrenergic Constriction in Muscle and Noncholinergic Dilatation in Dog'S Paw

01 Aug 1970-Circulation Research (Lippincott Williams & Wilkins)-Vol. 27, Iss: 2, pp 259-276
TL;DR: The results indicate that stimulation of carotid and aortic chemoreceptors activates selectively efferent adrenergic constrictor fibers supplying prevenous resistance vessels in the gracilis muscle and venous resistance Vessels in the paw.
Abstract: Experiments were done to characterize the vascular responses to stimulation of aortic and carotid chemoreceptors and to identify the efferent components of the sympathetic system which are activated in different vascular beds. The chemoreceptors were stimulated with nicotine and cyanide in anesthetized and artificially ventilated dogs. The gracilis muscle and hindpaw were isolated and perfused with blood at constant flow. Changes in perfusion pressure reflected changes in total vascular resistance, and changes in small vein pressure reflected changes in venous resistance. The results indicate that stimulation of carotid and aortic chemoreceptors activates selectively efferent adrenergic constrictor fibers supplying prevenous resistance vessels in the gracilis muscle and venous resistance vessels in the paw. In contrast, there was a dilatation of prevenous resistance vessels in the paw caused by activation of efferent sympathetic dilator fibers and not by withdrawal of sympathetic constrictor tone. The dilatation was not mediated through the release of acetylcholine, histamine, or bradykinin nor through beta receptors. Bilateral denervation of the carotid sinus and body and bilateral vagotomy abolished the reflex responses caused by injections of the chemicals. These responses were not the result of activation of baroreceptors since they were not reproduced during electrical stimulation of the carotid sinus nerve.
Citations
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Journal ArticleDOI
TL;DR: It is concluded that baroreflex activation selectively abolishes the SNA response to hypoxia but not to hypercapnia or the cold pressor test.
Abstract: Animal studies have demonstrated that activation of the baroreflex by increases in arterial pressure inhibits cardiovascular and ventilatory responses to activation of peripheral chemoreceptors (PC) with hypoxia. In this study, we examined the influences of baroreflex activation on the sympathetic response to stimulation of PC and central chemoreceptors in humans. PC were stimulated by hypoxia (10% O2/90% N2) (n = 6) and central chemoreceptors by hypercapnia (7% CO2/93% O2) (n = 6). Responses to a cold pressor stimulus were also obtained as an internal reflex control to determine the selectivity of the interactive influence of baroreflex activation. Baroreflex activation was achieved by raising mean blood pressure by greater than 10 mmHg with intravenous infusion of phenylephrine (PE). Sympathetic nerve activity (SNA) to muscle was recorded from a peroneal nerve (microneurography). During hypoxia alone, SNA increased from 255 +/- 92 to 354 +/- 107 U/min (P less than 0.05). During PE alone, mean blood pressure increased and SNA decreased to 87 +/- 45 U/min (P less than 0.05). With hypoxia during baroreflex activation with PE, SNA did not increase (50 +/- 23 U/min). During hypercapnia alone, SNA increased from 116 +/- 39 to 234 +/- 72 U/min (P less than 0.01). Hypercapnia during baroreflex activation with PE increased SNA from 32 +/- 25 U/min during PE alone to 61 +/- 26 U/min during hypercapnia and PE (P less than 0.05). Like hypercapnia (but unlike hypoxia) the cold pressor test also increased SNA during PE. We conclude that baroreflex activation selectively abolishes the SNA response to hypoxia but not to hypercapnia or the cold pressor test. The inhibitory interaction of the baroreflex and the peripheral chemoreflex may be explained by convergence of baroreceptor and peripheral chemoreceptor afferents on neurons in the medulla.

370 citations

Journal ArticleDOI
TL;DR: The peripheral and central chemoreflexes have powerful effects on sympathetic activity in both health and disease and may contribute importantly to disease pathophysiology, particularly in conditions such as hypertension, obstructive sleep apnoea and heart failure.
Abstract: The chemoreflexes are important modulators of sympathetic activation. The peripheral chemoreceptors located in the carotid bodies respond primarily to hypoxaemia. Central chemoreceptors located in the region of the brainstem respond to hypercapnia. Activation of either the hypoxic or hypercapnic chemoreflex elicits both hyperventilation and sympathetic activation. During apnoea, when the inhibitory influence of stretch of the pulmonary afferents is eliminated, there is a potentiation of the sympathetic response to both hypoxia and hypercapnia. This inhibitory influence of the pulmonary afferents is more marked on the sympathetic response to peripheral compared with central chemoreceptor activation. The arterial baroreflexes also have a powerful inhibitory influence on the chemoreflexes. This inhibition is again more marked with respect to the peripheral compared with central chemoreflexes. In patients with hypertension, there is a marked increase in the sympathetic and ventilatory response to hypoxaemia. During apnoea, with elimination of the inhibitory influence of breathing, the sympathetic response in untreated mild hypertensive patients is strikingly greater than that seen in matched normotensive controls. This potentiated peripheral chemoreflex sensitivity in hypertension may be explained in part by impaired baroreflex function in these patients. Enhanced peripheral chemoreflex sensitivity is also evident in patients with obstructive sleep apnoea. This peripheral chemoreflex enhancement is not explained by obesity, as obese individuals have a selective potentiation of the central chemoreceptors with peripheral chemoreflex responses similar to those seen in lean controls. Increased sensitivity to hypoxaemia has important implications in patients with obstructive sleep apnoea who experience repetitive and severe hypoxaemic stress. Tonic activation of the chemoreflex may also contribute to the high levels of sympathetic activity evident even during normoxic daytime wakefulness in sleep apnoea patients. Administration of 100% oxygen in patients with sleep apnoea results in reductions in heart rate, blood pressure and central sympathetic outflow. In patients with heart failure, the central chemoreflex response to hypercapnia is markedly and selectively enhanced. This increased central chemoreflex sensitivity may contribute to the development of central sleep apnoea in heart failure patients. Administration of 100% oxygen does not lower sympathetic activity in patients with heart failure, providing further evidence against any peripheral chemoreflex potentiation. The peripheral and central chemoreflexes have powerful effects on sympathetic activity in both health and disease and may contribute importantly to disease pathophysiology, particularly in conditions such as hypertension, obstructive sleep apnoea and heart failure.

303 citations

Journal ArticleDOI
TL;DR: The chemoreceptor reflex is enhanced in borderline hypertensive subjects and results in exaggerated increases in sympathetic nerve activity during hypoxia, which may contribute to excess sympathetic activity in borderline hypertension subjects and to adverse consequences of sleep apnea in hypertensiveSubjects.
Abstract: We tested the hypothesis that sympathetic nerve responses to stimulation of chemoreceptors by hypoxia are exaggerated in borderline hypertensive humans. We compared responses to isocapnic hypoxia in eight borderline hypertensive subjects and eight normotensive control subjects matched for age, sex, weight, and height without a family history of hypertension. Measurements of heart rate, mean blood pressure, minute ventilation, and sympathetic nerve activity to muscle were made before and during hypoxia. We also measured responses to a period of voluntary apnea during hypoxia. There were no significant differences between the increases in heart rate, blood pressure, and ventilation in response to hypoxia in the two groups. However, during hypoxia sympathetic activity in the hypertensive subjects increased by 40.6 +/- 13.6% (mean +/- SE), greater than the increase of 20.4 +/- 5.0% in the control subjects (p less than 0.05). In six hypertensive and six control subjects, when apnea was performed during hypoxia, sympathetic activity increased by 605.0 +/- 294.3% in the hypertensive subjects and by only 52.8 +/- 17.3% in the control subjects (p less than 0.001). We conclude that the chemoreceptor reflex is enhanced in borderline hypertensive subjects and results in exaggerated increases in sympathetic nerve activity during hypoxia. This enhanced chemoreceptor reflex is especially obvious when the inhibitory influence of breathing and thoracic afferent activity is eliminated by apnea. This exaggerated response may contribute to excess sympathetic activity in borderline hypertensive subjects and to adverse consequences of sleep apnea in hypertensive subjects.

260 citations

OtherDOI
Carl F. Rothe1
TL;DR: The sections in this article are: Venous Return and Potential Role of Veins in Cardiovascular Homeostasis, Vascular Compliance and Capacitance, Pharmacology of Vein, and General Problems.
Abstract: The sections in this article are: 1 Synopsis 2 Perspectives 3 Definitions and Basic Concepts 3.1 Definitions 3.2 Active Contraction of Veins 3.3 Effect of Flow on Vascular Volume 3.4 Central Venous Pressure 3.5 Mean Circulatory Filling Pressure 3.6 Venous Hemodynamics 3.7 Venous Resistance 4 Structural Characteristics of Veins 4.1 Anatomy 4.2 Volume of Blood 4.3 Vascular Compliance 4.4 Linearity of Pressure-Volume Relationship 5 Venous Return and Potential Role of Veins in Cardiovascular Homeostasis 5.1 Guytonian Relationship Between Venous Return and Cardiac Output 5.2 De Jager-Krogh Phenomenon 5.3 Venous Pooling on Standing 6 Reflex Control of Capacitance System 6.1 Effect of Neural and Hormonal Stimulation 6.2 Baroreceptors 6.3 Chemoreceptors 6.4 Atrial, Ventricular, and Pulmonary Receptors 6.5 Receptor Interaction 6.6 Venous Myogenic Activity 6.7 Venoarteriolar Reflex 6.8 Effect of Temperature 6.9 Time Course of Reflex Response 6.10 Capacitance-Vessel Tone 7 Veins in Health and Disease 7.1 Exercise 7.2 Vasovagal Syncope 7.3 Orthostatic Hypotension 7.4 Shock 7.5 Hypertension 8 Methods of Measurement of Vascular Capacitance 8.1 Transmural Pressure of Capacitance Vessels 8.2 Volume of Capacitance Vessels 8.3 Measures of Total-Body Vascular Compliance and Capacitance 8.4 General Problems 9 Pharmacology of Veins 9.1 Anesthetics 9.2 Angiotensin 9.3 Catecholamines 9.4 Histamine 9.5 Morphine 9.6 Nitroprusside 9.7 Serotonin 9.8 Vasopressin 10 Future Research

207 citations

References
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Journal ArticleDOI
TL;DR: Experiments done between 1877 and 1926 showed that a rise of blood pressure in the carotid-cephalic circulation induces bradycardia and a fall of the systemic arterial pressure, while a drop in the vehicle pressure provokes acceleration of the heart rate and a rise in the systemicarterial pressure.
Abstract: After the discovery ofthe pulmonary circulation by Ibn-an-Nafis in the thirteenth century and by Servetus in the sixteenth century and the discovery of the systemic circulation of the blood by Harvey in 1628, arterial pressure was first measured by Stephen Hales in 1733 and then by Poiseuille in 1828 and Ludwig in 1847, wno recorded arterial blood pressure by means ofa glass tube or a mercury manometer connected with an artery. As a result of numerous observations, the physiologists concluded that the arterial pressure was subject to regulation and tried to clarify the mechanisms. In 1836 Astley Cooper observed that compression of both common carotid arteries, which induced a fall of arterial pressure in the head and brain, provoked acceleration of the heart rate and a rise in the systemic arterial pressure (1). This observation was confirmed by Magendie in 1838 (2). Experiments done between 1877 and 1926 by several workers (3-10) showed that a rise of blood pressure in the carotid-cephalic circulation induces bradycardia and a fall of the systemic arterial pressure, while a drop in the carotid-cephalic pressure provokes acceleration ofthe heart rate and a rise ofsystemic arterial pressure. All these experimental observations were considered to be a demonstration ofa direct sensitivity of the cardiovascular centers to blood pressure variations. The direct central regulation and homeostasis of arterial pressure by means of the action of blood pressure variations on the cardiovascular centers was thus generally accepted. But as early as 1900 Pagano (11) and Siciliano (12), of the laboratory of Spallitta in Palermo, published an interesting series of experiments. Siciliano showed that while clamping of both common carotid arteries induced tachycardia and a rise in the systemic arterial pressure, clamping of

902 citations


"Reflex Vascular Responses to Stimul..." refers background in this paper

  • ...Furthermore, Heymans and Neil have indicated that decrease of blood pressure at the carotid bifurcation may stimulate carotid chemoreceptors (13)....

    [...]

Journal ArticleDOI

232 citations


"Reflex Vascular Responses to Stimul..." refers background in this paper

  • ...The magnitude of this constrictor response is similar to that resulting from electrical stimulations equivalent to the physiologic range of impulse frequency obtained in sympathetic vasomotor fibers (14)....

    [...]

Journal ArticleDOI
TL;DR: The release ofbradykinin-forming enzyme from the perfused gland has been followed quantitatively, and the results show a consistent relationship between glandular activity, local vasodilatation and release of bradykinIn-forming enzymes.
Abstract: As a result of previous experiments on the submandibular salivary gland, it was concluded that functional hyperaemia in this organ is due to the vasodilator action of a material indistinguishable from bradykinin. This is formed in the interstitial fluid by the action on the plasma proteins of an enzyme-like substance escaping from the gland cells during activity (Hilton & Lewis, 1955a, b). In those experiments the enzyme was demonstrated in the effluent collected from the perfused gland activated by stimulation of the chorda tympani. In the present investigation we have examined the question whether this release is always obtained following glandular activity, no matter whether this is produced by chorda or sympathetic stimulation, or by injection of acetylcholine or sympathomimetic amines. The release ofbradykinin-forming enzyme from the perfused gland has been followed quantitatively, and the results show a consistent relationship between glandular activity, local vasodilatation and release of bradykinin-forming enzyme.

180 citations

Journal ArticleDOI
TL;DR: In dogs under chloralose and urethane anaesthesia, the carotid and aortic bodies were isolated from the circulation and separately perfused with blood, the composition of which could be controlled at will.
Abstract: 1. In dogs under chloralose and urethane anaesthesia, the carotid and aortic bodies were isolated from the circulation and separately perfused with blood, the composition of which could be controlled at will. The remainder of the systemic circulation was perfused at constant blood flow, thereby enabling the reflex vascular responses to be determined. The systemic venous blood was oxygenated in the isolated perfused lungs of a second dog and the PO2 and PCO2 of the systemic arterial blood was maintained constant. 2. Using hypoxic hypercapnic blood to stimulate the arterial chemoreceptors, carotid body excitation in spontaneously breathing animals caused an increase in respiratory minute volume approximately seven times larger than that evoked by stimulation of the aortic bodies. Whereas the hyperpnoea of carotid body origin is due to an increase in rate and depth of breathing, that from the aortic bodies is due predominantly to an increase in respiratory frequency. 3. Stimulation of the carotid bodies in spontaneously breathing animals caused small variable changes in systemic vascular resistance, whereas stimulation of the aortic bodies invariably increased the vascular resistance. 4. When pulmonary ventilation was maintained constant, the vascular response to stimulation of the carotid bodies was considerably modified in that constriction invariably occurred; that from the aortic bodies, however, was little affected. There was now no significant difference in the size of responses from the two groups of chemoreceptors. These constrictor responses represent the primary vascular effects. 5. A similar modification of the carotid body vascular response occurred in the spontaneously breathing animal after denervation of the lungs, and is due to abolition of a lung-inflation vasodilator reflex. 6. The size of the primary vasoconstrictor responses from the carotid and aortic bodies is reduced by lowering the arterial blood PCO2. 7. The results indicate that there is a fundamental difference in the functions of the carotid and aortic bodies. They exert a quantitatively similar primary control of the ‘vasomotor centre’ which is in striking contrast to the relatively more powerful influence on respiration by the carotid bodies. In the spontaneously breathing animal, however, the primary vasoconstrictor response from the carotid bodies is offset to a varying degree by the lung-inflation vasodilator reflex initiated by the concomitant hyperpnoea. This is not evident with the aortic bodies because of the relatively weaker respiratory response they evoke.

114 citations


"Reflex Vascular Responses to Stimul..." refers background in this paper

  • ...• The changes in total peripheral vascular resistance during stimulation of aortic or carotid chemoreceptors indicate that the predominant peripheral response is a vasoconstrictor one (1-4)....

    [...]

  • ...The reasons are: (1) similar responses in the muscle and paw were observed whether the arterial pressure fell (carotid stimulation) or increased (aortic stimulation); (2) marked bradycardia and hypotension could be produced by stimulation of the distal end of the right vagus and by stimulation of the carotid sinus nerve without triggering significant reflex responses such as those seen after by gest on N ovem er 2, 2017 http://circhajournals....

    [...]

Journal ArticleDOI
TL;DR: The findings indicate that hypoxic stimulation of the carotid bodies causes a dichotomous sympathetic response, that is, a reduction of sympathetic discharge to the heart and a simultaneous increase of sympathetic discharged to the peripheral vasculature.
Abstract: The hemodynamic responses to hypoxic stimulation of the carotid bodies were investigated in the dog with controlled respiration. A dual, rotating disc oxygenator system was utilized to perfuse the vascularly isolated carotid region alternately with blood of high or low pO2. Perfusion of the carotid bodies with hypoxic blood caused a large reduction of heart rate. The bradycardia response was reduced, but not abolished, by vagotomy. However, the subsequent administration of hexamethonium completely abolished the response. The contractility of the atrium was reduced by carotid body hypoxia, and varying degrees of heart block were frequently observed. These responses were abolished by vagotomy and considered to be due to efferent vagal activity. Ventricular function curves showed that carotid body hypoxia usually caused a reduction, never an increase, of ventricular contractility. This indicates a reduction of sympathetic discharge to the heart. The reduction in heart rate after vagotomy and the reduction in ventricular contractility were associated with a concomitant increase of total peripheral resistance. These findings indicate that hypoxic stimulation of the carotid bodies causes a dichotomous sympathetic response, that is, a reduction of sympathetic discharge to the heart and a simultaneous increase of sympathetic discharge to the peripheral vasculature. Systemic hypoxia caused an increase of both ventricular contractility and total peripheral resistance. Consequently, the hemodynamic responses to systemic hypoxia cannot be entirely ascribed to a primary chemoreceptor reflex from the carotid bodies. It is suggested that the cardiac sympathetic responses seen in systemic hypoxia are due, at least in part, to direct hypoxic stimulation of the central nervous system.

98 citations


"Reflex Vascular Responses to Stimul..." refers background in this paper

  • ...• The changes in total peripheral vascular resistance during stimulation of aortic or carotid chemoreceptors indicate that the predominant peripheral response is a vasoconstrictor one (1-4)....

    [...]

  • ...The reasons are: (1) similar responses in the muscle and paw were observed whether the arterial pressure fell (carotid stimulation) or increased (aortic stimulation); (2) marked bradycardia and hypotension could be produced by stimulation of the distal end of the right vagus and by stimulation of the carotid sinus nerve without triggering significant reflex responses such as those seen after by gest on N ovem er 2, 2017 http://circhajournals....

    [...]