Carotid body chemoreceptor activity in the new-born lamb

1. Tidal volume, carotid artery oxygen tension (P(a,O2)) and blood pressure and chemoreceptor activity in the sinus nerve have been continuously measured and recorded in nine lambs anaesthetized with pentobarbitone sodium, and varying in age from some minutes after birth to 5 days after birth.2. Inhalation of 100% oxygen caused, after a delay of 3-4 sec, a rise in P(a,O2), a fall in minute ventilation (V) and chemoreceptor activity. The respiratory response was abolished after section of both sinus nerves.3. Inhalation of 10% oxygen in nitrogen caused a fall in carotid P(a,O2), a rise in respiration and in chemoreceptor activity. The respiratory response was abolished after both sinus nerves had been cut.4. Minute ventilation, carotid P(a,O2) and chemoreceptor activity increased on breathing 5% CO(2) in air. Section of both sinus nerves did not affect the maximum increase in ventilation but the lag of the respiratory response approximately doubled while respiration increased more slowly.5. From these results, it was calculated that the chemoreceptors had a latency of 0.25-0.5 sec and the time constant of the rate of change of chemoreceptor activity was 10-15 sec.6. The chemoreceptors responded to changes in P(a,O2) of +/-5-10 mm Hg.7. Comparison of these results with those reported in adult animals suggest that the peripheral chemoreceptors are fully mature at birth, that their response does not differ with the age of the lamb and that the carotid body chemoreceptors are concerned both in the mediation of the hypoxic drive to ventilation and in the respiratory response to inhaled CO(2).     

Comparison of the reflex responses elicited by stimulation of the separately perfused carotid and aortic body chemoreceptors in the dog

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 P(O2) and P(CO2) 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 P(CO2).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.     

Amplitude dependence of the carotid sinus reflex

Summary Both carotid arteries of anesthetized mongrel dogs were perfused with arterial blood by a servo controlled peristaltic pump. This preparation allowed to examine the carotid sinus pressure reflex under open loop condition as well as under closed loop condition, without touching the receptor area. The experiments were performed before and after vagotomy. The response of the systemic arterial pressure to changes of the carotid sinus pressure was recorded and evaluated. In order to test the open loop characteristics of the system, the perfusion pressure in the carotid arteries was varied sinusoidally (0.01 to 0.2 Hz). It was found that the amplitude of the carotid sinus pressure had a marked influence on the gain of the reflex. The gain decreased with increasing amplitudes of the carotid sinus pressure at all frequencies tested. Vagotomy increased the gain especially at the low frequencies.By applying a hybrid computer system to control the perfusion pump, the same preparation could be examined under closed loop condition. Particularly, the effect of an artificial time delay (1–35 sec) between systemic and carotid sinus pressure was tested. We found that this procedure generates autooscillations of the arterial pressure. The period of the oscillations is proportional to the artificial time delay. From open loop results the closed loop behaviour of the system was calculated and compared with the actual experimental results. We could show that the amplitude dependence of the carotid sinus pressure reflex is important to explain the generation of oscillations in the closed loop system by an artificial time delay. However, whereas the predicted autooscillation frequencies agreed quite well with the experimental recordings, the prediction of the amplitudes of the oscillations showed remarkable errors, which probably are due to still unexplained nonlinearities.It can be concluded that 1) the amplitude dependence of the carotid sinus reflex is an important property of the pressure control system. 2. The application and comparison of open loop and closed loop methods in the same experiment allows to check results and predictions more thoroughly than either one of these methods alone.Supported by NIH grants HE 11747 and GM 1919 and Österreichischer Fonds zur Förderung der wissenschaftlichen Forschung.Supported by NIH research career development award HE 50288-01.     

The role of the carotid body chemoreceptors and carotid sinus baroreceptors in the control of cerebral blood vessels

1. Cerebral blood flow was measured in 17 baboons, anaesthetized with pentobarbitone, paralysed with gallamine and mechanically ventilated and in which the right sinus and both aortic nerves had been cut and the left carotid sinus vascularly isolated. Later in each experiment, the head was artificially perfused with femoral arterial blood via the innominate artery.2. Stimulation of the carotid body chemoreceptors with venous blood invariably caused a rise in regional cerebral blood flow whether the head was naturally or artificially perfused. This response was almost completely abolished if the VIIth cranial nerves were cut intracranially.3. Regional cerebral blood flow varied inversely with carotid sinus pressure.4. After the remaining (left) sinus nerve had been cut, the cerebral vascular response to hypoxia was negligible and the response to hypercapnia was markedly reduced. Blood flow then varied with perfusion pressure.5. These results provide further evidence that cerebral blood vessels are reflexly controlled and that the peripheral arterial receptors are involved. Their action is most conspicuous in the vascular response to hypoxia and together with intrinsic factors in the cerebral vascular bed, they determine the size of the vascular response to changes in CO(2) and pressure.     

Über die Wirkung der Pressoreceptoren des Carotisgebiets der narkotisierten Katze auf die Atmung nach isolierter Ausschaltung der Chemoreceptoren

1. In 5 cats ligthly anesthetized with chloralose-urethane all chemoreceptor response was abolished by cutting the vagosympathetic trunks including depressor nerves and by embolization of the carotid bodies by lycopodium powder. By means of a pressurized bottle attached to the femoral arteries mean arterial pressure was regulated to three different levels (160, 120 and 80 Torr consecutively) and was kept constant at each of these levels. Transients and steady state values of ventilation were recorded during this stepwise change of blood pressure. The effect on ventilation of severing sinus nerves at constant blood pressure was observed.After severing sinus nerves recording of the effect of blood pressure changes on ventilation was repeated.2. In this preparation (chemoreceptors denervated, carotid pressoreceptors intact) severing sinus nerves is followed by a diminution of ventilation in the same order of magnitude as described in the preceding papers, even if blood pressure is kept constant.3. Following stepwise diminution of mean arterial pressure in the chemodenervated cat, ventilation returns to its initial value after a transient increase. This confirms the conclusion of the preceding paper that during steady state no tonic influence of pressoreceptors on ventilation can be observed.4. The transient increase of ventilation following diminution of blood pressure is less pronounced, but not abolished, after severing the sinus nerves. It is therefore considered to be only partly due to the release of an inhibition by pressoreceptor impulses. The remaining effect must be due to other causes, possibly transient change of cerebral circulation.5. From this evidence and that from the preceding papers it must be concluded that the steady state decrease of ventilation observed after severing sinus nerves in cats inhaling gas mixtures containing 35 or 99% O₂ can not be attributed either to chemoreceptor drive by O₂ deficiency or to blood pressure effects on chemo—or pressoreceptors. Effects of CO₂ or H⁺ on chemoreceptors can be excluded as well since in the experiments of this paper all chemoreceptor drive is abolished.It must therefore be concluded that an unknown respiratory drive is depending upon the integrity of the sinus nerves.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

The role of the solitary and paramedian reticular nuclei in mediating cardiovascular reflex responses from carotid baro- and chemoreceptors

1. With dye-filled micro-electrodes single neurones in the medulla of anaesthetized paralysed cats were identified which: (a) fired rhythmically in synchrony with or were modulated by the cardiac cycle, and which ceased firing with occlusion of the ipsilateral common carotid artery (carotid sinus baroreceptor neurones); (b) were excited by stimulation of carotid body chemoreceptors by close intra-arterial injection of lobeline into the thyroid artery (carotid body chemoreceptor neurones).2. Twelve carotid baroreceptor neurones were identified, in thirty-three cats, nine of which were localized in the intermediate area of the nucleus of the solitary tract (NTS) within 1 mm ahead of or behind the obex; three units were located either in the parahypoglossal area or the dorsal portion of the paramedian reticular nucleus (PRN).3. Of the twenty-one carotid chemoreceptor neurones which were identified, thirteen were localized in the NTS, three in the parahypoglossal area and four in the dorsal PRN.4. Bilateral lesions of the paramedian reticular area of medulla destroying the PRN, abolished or reversed the depressor response to electrical stimulation of myelinated fibres of the carotid sinus nerve (CSN), attenuated the depressor response to carotid sinus stretch and augmented the pressor response to chemoreceptor stimulation by lobeline. Such lesions did not significantly alter the reflex heart rate responses.5. Small lesions of the NTS within an area 1 mm rostral to the obex abolished all reflex blood pressure and heart rate responses to electrical stimulation of the CSN or natural stimulation of carotid baro- or chemoreceptors.6. Baroreceptors and chemoreceptors of the CSN project both to the intermediate zone of the NTS and to more medial areas of the medulla, particularly the dorsal PRN and parahypoglossal area.7. The PRN serves to mediate the reflex depressor, but not cardio-vagal, response from myelinated baroreceptors and buffers the pressor responses from chemoreceptors; it may serve as an important area integrating cardiovascular activity descending from forebrain, brain stem and cerebellum with baroreceptor reflexes.8. Cardiovascular reflex responses arising from non-myelinated baroreceptors and all chemoreceptors are mediated by neurones in the intermediate area of the NTS.     

Effect of Carotid Sinus Stimulation on Cardiac Output and Peripheral Vascular Resistance during Changes in Blood Volume Distribution in Man

In ten healthy subjects (mean age 29.6 years) the hemodynamic response to carotid sinus stimulation (neck suction - 40 mmHg) was studied under control conditions and during peripheral pooling of blood (lower body negative pressure). Heart rate, arterial and central venous pressure, cardiac output and forearm blood flow were measured. The time sequence of the heart rate response was studied separately in six healthy subjects. During control conditions, carotid sinus stimulation induced a significant decrease in arterial pressure and heart rate. The blood pressure decrease mainly reflected a reduction in cardiac output, total peripheral vascular resistance being essentially unchanged. However, in the skeletal muscle, represented by a forearm segment, vascular resistance decreased significantly. During lower body negative pressure (LBNP) the same stimulation of the carotid sinus induced a significantly greater fall in mean arterial pressure even though the reduction in cardiac output was slightly smaller on the average than in the control condition. The heart rate increased, probably secondary to a time dependent increase in heart rate elicited by the continuous LBNP stimulus. Total peripheral vascular resistance decreased significantly during LBNP, the reaction likewise differing significantly from that in the control condition. Thus the augmented blood pressure response was due to a more pronounced vasodilatation when the carotid sinus was stimulated during lower body negative pressure. The results indicate that the hemodynamic changes elicited by carotid sinus stimulation are modified by changes in the distribution of blood volume and in the tone of resistance vessels.     

Partial blockade of skeletal muscle somatosensory afferents attenuates baroreflex resetting during exercise in humans

During exercise, the carotid baroreflex is reset to operate around the higher arterial pressures evoked by physical exertion. The purpose of this investigation was to evaluate the contribution of somatosensory input from the exercise pressor reflex to this resetting during exercise. Nine subjects performed seven minutes of dynamic cycling at 30 % of maximal work load and three minutes of static one-legged contraction at 25 % maximal voluntary contraction before (control) and after partial blockade of skeletal muscle afferents with epidural anaesthesia. Carotid baroreflex function was assessed by applying rapid pulses of hyper- and hypotensive stimuli to the neck via a customised collar. Using a logistic model, heart rate (HR) and mean arterial pressure (MAP) responses to carotid sinus stimulation were used to develop reflex function stimulus-response curves. Compared with rest, control dynamic and static exercise reset carotid baroreflex-HR and carotid baroreflex-MAP curves vertically upward on the response arm and laterally rightward to higher operating pressures. Inhibition of exercise pressor reflex input by epidural anaesthesia attenuated the bi-directional resetting of the carotid baroreflex-MAP curve during both exercise protocols. In contrast, the effect of epidural anaesthesia on the resetting of the carotid baroreflex-HR curve was negligible during dynamic cycling whereas it relocated the curve in a laterally leftward direction during static contraction. The data suggest that afferent input from skeletal muscle is requisite for the complete resetting of the carotid baroreflex during exercise. However, this neural input appears to modify baroreflex control of blood pressure to a greater extent than heart rate.     

Barosensory neurons in the ventrolateral medulla in rabbits and their responses to various afferent inputs from peripheral and central sources

In 55 anesthetized and paralyzed adult rabbits, 161 spontaneously active neurons which responded to electrical stimulation of A-fibers of the aortic nerve were found within the ventrolateral medulla (VLM). They were termed barosensory VLM neurons, since the aortic nerve A-fibers were considered to consist exclusively of afferents from arterial baroreceptors. Forty percent of barosensory VLM neurons tested (49/123) were activated antidromically by stimulation of the dorsolateral funiculus indicating that they send descending bulbospinal projections. Spontaneous discharges of barosensory VLM neurons were invariably inhibited by stimulation of aortic nerve A-fibers. Ninety-three percent of 80 neurons tested also responded to stimulation of aortic nerve C-fibers, a mixture of barosensory and nonbarosensory afferents. Natural stimulation of carotid sinus baroreceptors by an intravenous injection of phenylephrine in 19 vagotomized rabbits with aortic nerves disrupted inhibited spontaneous activity of all the 50 barosensory VLM neurons tested. By contrast, pharmacological stimulation of right or left carotid body chemoreceptors by close arterial injection of NaCN into the carotid sinus augmented activity of 93% of barosensory VLM neurons tested (41/44). The neuronal response was always greater to stimulation of chemoreceptors in the contralateral carotid sinus. Seven out of 8 barosensory VLM neurons tested (88%) were orthodromically excited by stimulation of the posterior hypothalamic area. In 74% of the 97 neurons examined in 29 vagotomized animals, a distinct respiratory-related rhythm, locked to that of phrenic nerve activity, was discerned. Thus, spontaneous activity of barosensory VLM neurons is inhibited by afferent inputs from aortic and carotid sinus baroreceptors, but is excited by incoming signals from carotid body chemoreceptors and the posterior hypothalamic area. It is also subject to the influence of the central mechanism generating the respiratory rhythm.     

Circulatory control in hypoxia by the sympathetic nerves and adrenal medulla

1. The effects of severe arterial and primary tissue (carbon monoxide) hypoxia on cardiac output, arterial and right atrial pressures, heart rate and ventilation, have been studied in unanaesthetized normal rabbits, and in animals subjected to adrenalectomy, ;sympathectomy' (guanethidine), adrenalectomy + ;sympathectomy', and section of the carotid sinus and aortic nerves.2. In both arterial and primary tissue hypoxia the sympathetic nerves play a more important part in the normal circulatory response than the adrenal medullary hormones.3. Provided one adrenergic effector pathway remains intact, animals with intact chemoreceptors and baroreceptors tolerate both types of hypoxia well. Circulatory control during both types of hypoxia by means of sympathetic nerves alone produces relatively more peripheral vasoconstriction than is observed during reflex control through increased adrenal catecholamine secretion.4. The occurrence of tonic sympathetic activity in animals with section of carotid sinus and aortic nerves permits maintenance of a high cardiac output during hypoxia but the arterial pressure is low and there is probably less selective distribution of blood flow to the periphery than in animals with normal reflex control.5. Absence of any adrenergic activity in adrenalectomized and ;sympathectomized' animals results in a gradual fall in cardiac output during prolonged hypoxia, after an initial small rise.6. The results in guanethidine-treated animals suggest that the sympathetic discharge to the arterial chemoreceptors is a factor sustaining chemoreceptor discharge during prolonged arterial hypoxia.     

Left ventricular inotropic and peripheral vasomotor responses from independent changes in pressure in the carotid sinuses and cerebral arteries in anaesthetized dogs

1. The pressure perfusing the isolated carotid sinuses and the pressure perfusing the cerebral circulation were changed independently, and the resulting inotropic responses in the left ventricle and peripheral vasomotor responses were determined.2. Inotropic responses were assessed by measuring changes in the maximum rate of change of left ventricular pressure (dP/dt max) with heart rate and mean aortic pressure held constant. Vascular resistance changes were usually assessed by perfusing the descending thoracic aorta at constant flow and measuring changes in perfusion pressure.3. Decreases in carotid sinus pressure over the baroreceptor sensitivity range resulted in a 45% increase in dP/dt max and a 59% increase in vascular resistance.4. Unless arterial oxygen tension was abnormally low, lowering cerebral perfusion pressure to 50 mm Hg resulted in little or no inotropic and vasomotor responses. In the presence of hypoxaemia (P(a,O2) < 60 mm Hg), lowering cerebral perfusion pressure to below about 80 mm Hg resulted in marked responses.5. These experiments suggest that, unless arterial oxygen tension is abnormally low, the carotid sinus reflex and not cerebral hypotension is important in the control of the inotropic state of the heart and of vasomotor activity. With hypoxaemia, responses from cerebral hypotension may also be important.     

Reflex Plasma Hyperglycemia and Hyperosmolality Evoked by Unloading of the Carotid Baroreceptors

Hemorrhage is usually accompanied by a considerable increase in the plasma osmolality and glucose concentration due to an augmented release of glucose from the liver. In the present cat experiments an attempt was made to investigate the possible role of different vascular receptors in mediating this hyperglycemic (hyperosmolar) response. Bilateral vagotomy or stimulation of the carotid chemoreceptors by perfusion of the carotid sinus with venous blood at normal pressure only slightly increased the arterial plasma glucose concentration. On the other hand, when the sinus nerves were cut in the vagotomized animal, thereby simulating complete unloading of the carotid baroreceptors, the arterial plasma glucose concentration rose by about 8 mM/L and the arterial plasma osmolality by about 10 mOsm/kg H₂O. Perfusion of the carotid baroreceptors with arterial blood at different levels of hypotension showed that the baroreceptor-induced hyperglycemia was graded in relation to the pressure level. Regional hypotension of the liver, pancreas, intestine, kidneys or brain did not significantly affect plasma glucose concentration or osmolality. We conclude that the reflex release of glucose from the liver during hemorrhage mainly is initiated from the unloading of arterial baroreceptors.     

Denervation of Carotid Baro- and Chemoreceptors in Humans

Experimental denervation in animals has shown that carotid baro- and chemoreceptors play an eminent role in maintaining blood pressure and blood gas homeostasis. Denervation of carotid sinus baro- and chemoreceptors in humans may occur as a complication of invasive interventions on the neck or after experimental surgical treatment in asthma. In this topical review, the short- and long-term effects of carotid baro- and chemoreceptor denervation on the control of circulation and ventilation in humans are discussed. Carotid baroreceptor denervation in humans causes a persistent decrease in vagal and sympathetic baroreflex sensitivity and an increase in blood pressure variability; however, carotid denervation does not lead to chronic hypertension. Therefore, although carotid baroreceptors contribute to short-term blood pressure control, other receptors are able to maintain normal chronic blood pressure levels in the absence of carotid baroreceptors. Conversely, carotid chemoreceptor denervation leads to permanent abolition of normocapnic ventilatory responses to hypoxia and reduced ventilatory responses to hypercapnia.     

An integrated model of the human ventilatory control system: the response to hypercapnia.

This work presents a mathematical model of the human respiratory control system, based on physiological knowledge. It includes three compartments for gas storage and exchange (lungs, brain tissue and other body tissues), and various kinds of feedback mechanisms. These comprehend peripheral chemoreceptors in the carotid body, central chemoreceptors in the medulla and a central ventilatory depression. The latter acts by reducing the response of the central neural system to the afferent peripheral chemoreceptor activity during prolonged hypoxia of the brain tissue. Furthermore, the model considers local blood flow adjustments in response to O2 and CO2 arterial pressure changes. In this study, the model has been validated by simulating the response to square changes in alveolar PCO2, performed at different constant levels of alveolar PO2. A good agreement with data reported in the literature has been checked. Subsequently, a sensitivity analysis on the role of the main feedback mechanisms on ventilation response to CO2 has been performed. The results suggest that the ventilatory response to CO2 challenges during hyperoxia can be almost completely ascribed to the central chemoreflex, while, during normoxia, the peripheral chemoreceptors provide a modest contribution too. By contrast, the response to hypercapnic stimuli during hypoxia involves a complex superimposition among different factors with disparate dynamics. Hence, results suggest that the ventilatory response to hypercapnia during hypoxia is more complex than that provided by simple empirical models, and that discrimination between the central and peripheral components based on time constants may be misleading.     

The contribution of the arterial chemoreceptors to the stimulation of respiration by adrenaline and noradrenaline in the cat

1. Intravenous infusions of adrenaline and noradrenaline in doses averaging 0.8 mug/kg.min increased the respiratory minute volume of anaesthetized cats breathing room air. The mean increase in respiratory minute volume was 14% during adrenaline infusion and 8% during noradrenaline infusion.2. In a small group of decerebrate cats infusions of adrenaline and noradrenaline increased ventilation by 19 and 27% respectively.3. Intravenous catecholamine infusions also increased the respiratory responses of anaesthetized animals to the inhalation of 5% or 10% O(2) in N(2) and to the inhalation of 5% CO(2) in air.4. Adrenaline and noradrenaline infusions had no significant effect on the ventilation of animals breathing 100% O(2), nor did they significantly alter the respiratory response to the inhalation of 5% CO(2) in O(2).5. After section of the carotid sinus and aortic nerves, a blood-pressure compensator being used to minimize changes in arterial pressure, catecholamines had no effect on the respiration of cats breathing air.6. An increase in carotid body chemoreceptor discharge accompanied the increase in ventilation during catecholamine infusion.7. Intravenous catecholamine infusions still produced an increase in ventilation and carotid body chemoreceptor discharge after both aortic nerves and both cervical sympathetic nerves had been cut.8. Intra-arterial infusions into one carotid artery of 0.2 mug/kg.min of adrenaline or 0.1 mug/kg.min of noradrenaline led to mean increases in respiratory minute volume of 9.9 and 11.5% respectively. No increase occurred after section of the corresponding carotid sinus nerve. Such infusions also evoked an increase in carotid body chemoreceptor discharge.9. It is concluded that the hyperpnoea produced by adrenaline and noradrenaline infusions in the cat is predominantly reflex in origin and is mediated by the arterial chemoreceptors.10. The increase in ventilation produced by adrenaline appears to have a component additional to its effect upon the chemoreceptors though the nature of this action has not been identified.     

Analysis of Interoceptive Reflexes in Experimental Tuberculosis

Summary It was shown that in its common effect upon healthy cats, tuberculin first of all inhibits reflexes arising from the chemoreceptors. This effect was most marked in perfusion experiments on the intestine, as well as in experiments with the carotid sinus reflex. Inhibition of reflexes from mechanoreceptors of the urinary bladder was less marked. The assumption is made that in its general effect, tuberculin inhibits the central neural elements of the afferent section of the reflex arc associated with tissue chemoreceptors.Presented by V. N. Chernigovsky, Active Member of the Academy of Medical Sciences, USSR     

Interplay among carotid sinus, cardiopulmonary, and carotid body reflexes in dogs.

Interactions among vascular reflexes evoked from carotid sinuses, carotid bodies, and cardiopulmonary region were examined in anesthetized, atropinized, and respired dogs with aortic nerves cut. The carotid sinuses were perfused at 220, 150, and 40-50 mmHg; the chemoreceptors were stimulated by perfusion with hypoxic hypercapnic blood. Cardiopulmonary vasomotor inhibition was interrupted by vagal cold block. Measurements were made of arterial blood pressure and of kidney and hindlimb vascular resistance. At sinus pressures less than 170-160 mmHg, cardiopulmonary vasomotor inhibition increased with increase in blood volume. At high sinus pressure, interruption of this augmented cardiopulmonary inhibition was as ineffective in changing vascular resistance as interruption of the lesser inhibition present during normovolemia. Chemoreceptor stimulation increased the response to vagal block at intermediate but not at high or low sinus pressure. The studies demonstrate the dominant role of the carotid sinus reflex when the three systems interact and the ineffectiveness of chemoreceptor stimulation when carotid or cardiopulmonary inhibition is maximal.     

Effect of CO2 on the systemic and coronary circulations and on coronary sinus blood gas tensions.

The responses to hypocapnia and to hypercapnia of both the systemic and the coronary circulations have been studied in the dog during intermittent positive pressure ventilation under halothane anaesthesia. In the absence of significant variations of myocardial contractility, the reduction of cardiac output, because of hypocapnia, was determined by the increase of systemic vascular resistance, while the increase of cardiac output because of hypercapnia was determined by an increase of heart rate without change of stroke volume. The alterations of coronary blood flow (reduction following hypocapnia, augmentation following hypercapnia) were considerably larger than the changes of cardiac output and of myocardial oxygen consumption. Such disparity between oxygen supply and demand, together with the effect of pH and PCO2 on the oxyhaemoglobin dissociation curve led to a marked reduction of coronary sinus PO2 in response to hypocapnia and a marked increase of coronary sinus PO2 in response to hypercapnia. The data suggests that PCO2 (or respiratory alterations of pH) may have a direct effect on the regulation of coronary blood flow. The low coronary sinus PO2 observed at hypocapnia may suggest the risk of myocardial ischaemia.     

Baroreceptor and somatic sensory regulation of kidney function in two-kidney, one-clip Goldblatt hypertensive rats.

The aim of this investigation was to characterize the renal haemodynamic and tubular responses to somatic afferent nerve stimulation following the removal of afferent nerve input from the atria or the carotid sinuses in chloralose-urethane-anaesthetized Sprague-Dawley rats and two-kidney, one-clip Goldblatt hypertensive rats. Bilateral stimulation of the brachial nerve plexi at 15 V, 1.3 Hz for 0.2 ms resulted in an increase in systemic blood pressure in each group of 10-40%, while renal perfusion pressure was maintained at a constant level. There were significantly larger falls in left renal blood flow and combined left and right glomerular filtration rate in all groups following selective denervation of either the cardiopulmonary or the carotid sinus baroreceptors, respectively. Brachial nerve stimulation decreased urine flow rate and absolute and fractional sodium excretion from both kidneys in Sprague-Dawley intact animals by 53, 65 and 59%; in vagotomized animals by 68, 77 and 63%; and in carotid sinus denervated animals by 86, 90 and 48%, respectively. The renal response in the Goldblatt group were similar to the normotensive group, but the main contribution of the total response was from the untouched left kidney. The inhibitory influence of the vagus and carotid sinuses on the renal sympathetic nerve-mediated sodium and water resorption appeared to be enhanced in the Goldblatt hypertensive rats when compared with the normotensive rats. The renal functional responses to somatic afferent nerve stimulation appeared to be well preserved in the renovascular hypertensive rats, although there were important differences in the contributions to the responses from the left and right kidneys. Furthermore, the baroreceptors exerted a greater influence on basal renal function in the hypertensive rats.     

Effects of graded pulsatile pressure on the reflex vasomotor responses elicited by changes of mean pressure in the perfused carotid sinus-aortic arch regions of the dog

1. In the anaesthetized dog, the carotid sinuses and aortic arch were isolated from the circulation and separately perfused with blood by a method which enabled the mean pressure, pulse pressure and pulse frequency to be varied independently in each vasosensory area. The systemic circulation was perfused at constant blood flow by means of a pump and the systemic venous blood was oxygenated by an extracorporeal isolated pump-perfused donor lung preparation.2. We have confirmed our previous observations that under steadystate conditions the vasomotor responses elicited reflexly by changes in mean carotid sinus pressure are modified by alterations in carotid sinus pulse pressure, whereas those evoked by changes of mean aortic arch pressure are only weakly affected by modifications of aortic pulse pressure.3. When the carotid sinus and aortic arch regions are perfused in combination at constant pulse frequency (110 c/min), the relationship between mean carotid sinus-aortic arch pressure and systemic arterial perfusion pressure is dependent on the size of the pulse pressure.4. Increasing the pulse pressure alters the curve relating the mean carotid sinus-aortic arch pressure to systemic arterial perfusion pressure in such a way that the perfusion pressure is lower at a given carotid sinus-aortic arch pressure within the range 80-150 mm Hg. The larger the pulse pressure, up to about 60 mm Hg, the greater the fall in systemic arterial perfusion pressure. Above a mean carotid sinus-aortic arch pressure of about 150 mm Hg, alterations of pulse pressure have little effect.5. There is a family of curves representing the relation between mean carotid sinus-aortic arch pressure and systemic vascular resistance, depending on the pulse pressure.