The site of action of nerves in the pulmonary vascular bed in the dog

1. The effects of stimulation of the thoracic vagosympathetic nerve or upper thoracic sympathetic chain on the pulmonary vascular resistance have been studied in atropinized, isolated, ventilated lung lobes under various conditions of pulmonary circulation perfusion. Throughout the nerve-stimulation tests bronchial circulation perfusion was maintained or temporarily interrupted.2. The pulmonary vascular resistance increase evoked by nerve stimulation (a) occurred in the absence of tidal air changes; (b) did not consistently differ during predominantly ;sluice' and ;non-sluice' conditions of pulmonary circulation perfusion; (c) was approximately one and a half times greater during constant pressure than during constant volume inflow perfusion of the pulmonary circulation; and (d) was greater during reverse than during forward perfusion.3. In lung lobes perfused in either direction at constant volume inflow nerve stimulation produced an increase in inflow pressure and a diminution in total lung blood volume reflected by a temporary increase in blood outflow.4. In lung lobes in which neither the pulmonary nor the bronchial circulations were perfused and the capillaries were completely blocked by high intratracheal pressures, thus isolating the pulmonary arterial system from the venous system, nerve stimulation produced a diminution in the blood volume of both systems.5. Nerve stimulation produced a rise in bronchial arterial pressure in the absence of pulmonary circulation perfusion.6. Further evidence is adduced that pulmonary vasomotor nerve responses do not depend upon the transfer of transmitter substances from the bronchial to the pulmonary circulation.7. The possible significance of these observations in relation to the site of action of pulmonary vasomotor nerves is discussed.     

An analysis of the reflex systemic vasodilator response elicited by lung inflation in the dog

1. A maintained inflation of the lungs caused a reflex reduction in total systemic vascular resistance in anaesthetized dogs under conditions in which the systemic circulation was perfused at constant blood flow and the arterial blood P(O2) and P(CO2) were maintained constant.2. The fall in systemic arterial perfusion pressure evoked by inflation of the lungs was accompanied by an increase in blood flow to the lower limbs and a reduction in their calculated vascular resistance. Since the fall in resistance occurred when the limb was perfused either at constant pressure or at constant blood flow, it must be due to vasodilatation.3. Lung inflation caused vasodilatation in skin, muscle, and in the splanchnic vascular bed. The responses in vertebral circulation were, however, small and variable.4. The vasodilator responses in the vascular territories studied were reflex in nature, being abolished by cutting the cervical vagosympathetic nerves, in which run the afferent fibres, or by interrupting the sympathetic pathways to the blood vessels.5. In the intact limb, muscle, skin and splanchnic vascular bed, the vasodilator responses to lung inflation were unaffected by atropine or propranolol, but were abolished by hexamethonium, dibenyline and bretylium tosylate, indicating that they were due predominantly to a reduction in the activity in sympathetic adrenergic vasoconstrictor fibres.     

Reflex responses from the main pulmonary artery and bifurcation in anaesthetised dogs

This study was undertaken to determine the reflex cardiovascular and respiratory responses to discrete stimulation of pulmonary arterial baroreceptors using a preparation in which secondary modulation of responses from other reflexes was prevented. Dogs were anaesthetised with -chloralose, artificially ventilated, the chests widely opened and a cardiopulmonary bypass established. The main pulmonary arterial trunk, bifurcation and extrapulmonary arteries as far as the first lobar arteries on each side were vascularly isolated and perfused through the left pulmonary artery and drained via the right artery through a Starling resistance which controlled pulmonary arterial pressure. Pressures distending systemic baroreceptors and reflexogenic regions in the heart were controlled. Reflex vascular responses were assessed from changes in perfusion pressures to a vascularly isolated hind limb and to the remainder of the subdiaphragmatic systemic circulation, both of which were perfused at constant flows. Respiratory responses were assessed from recordings of efferent phrenic nerve activity. Increases in pulmonary arterial pressure consistently evoked increases in both perfusion pressures and in phrenic nerve activity. Both vascular and respiratory responses were obtained when pulmonary arterial pressure was increased to above about 30 mmHg. Responses increased at higher levels of pulmonary arterial pressures. In 13 dogs increases in pulmonary arterial pressure to 45 mmHg increased systemic perfusion pressure by 24 +/- 7 mmHg (mean +/- S.E.M.) from 162 +/- 11 mmHg. Setting carotid sinus pressure at different levels did not influence the vascular response to changes in pulmonary arterial pressure. The presence of a negative intrathoracic pressure of -20 mmHg resulted in larger vascular responses being obtained at lower levels of pulmonary arterial pressure. This indicates that the reflex may be more effective in the intact closed-chest animal. These results demonstrate that stimulation of pulmonary arterial baroreceptors evokes a pressor reflex and augments respiratory drive. This reflex is likely to be elicited in circumstances where pulmonary arterial pressure increases and the negative excursions of intrathoracic pressure become greater. They are likely, therefore, to be involved in the cardio-respiratory response to exercise as well as in pathological states such as pulmonary hypertension or restrictive or obstructive lung disease.     

Cardiovascular responses in apnoeic asphyxia: role of arterial chemoreceptors and the modification of their effects by a pulmonary vagal inflation reflex

1. In the spontaneously breathing anaesthetized dog, the systemic circulation was perfused at constant blood flow; there was no pulmonary blood flow and the systemic arterial blood P(O2) and P(CO2) were controlled independently by an extracorporeal isolated pump-perfused donor lung preparation. The carotid and aortic bodies were separately perfused at constant pressure with blood of the same composition as perfused the systemic circulation.2. Apnoeic asphyxia, produced by stopping the recipient animal's lung movements and, at the same time, making the blood perfusing the systemic circulation and the arterial chemoreceptors hypoxic and hypercapnic by reducing the ventilation of the isolated perfused donor lungs, caused an increase in systemic vascular resistance.3. While the systemic arterial blood was still hypoxic and hypercapnic, withdrawal of the carotid and aortic body ;drive' resulted in a striking reduction in systemic vascular resistance. Re-establishing the chemoreceptor ;drive' immediately increased the vascular resistance again.4. Apnoeic asphyxia carried out while the carotid and aortic bodies were continuously perfused with oxygenated blood of normal P(CO2) had little or no effect on systemic vascular resistance.5. The systemic vasoconstrictor response produced by apnoeic asphyxia was reduced or abolished by re-establishing the recipient animal's lung movements, and this effect occurred in the absence of changes in the composition of the blood perfusing the systemic circulation and arterial chemoreceptors. This abolition of the vasoconstriction was due to a pulmonary reflex.6. Apnoeic asphyxia slowed the rate of the beating atria due to excitation of the carotid and aortic body chemoreceptors. This response can be over-ridden by an inflation reflex arising from the lungs.7. It is concluded that the cardiovascular responses observed in apnoeic asphyxia are due, at least in part, to primary reflexes from the carotid and aortic body chemoreceptors engendered by arterial hypoxia and hypercapnia. The appearance of these responses is, however, dependent upon there being no excitation of a pulmonary (inflation) vagal reflex.     

Absence of reflex vascular responses from the intrapulmonary circulation in anaesthetised dogs

The aim of this investigation was to determine whether reflex cardiovascular responses were obtained to localised distension of the intrapulmonary arterial and venous circulations in a preparation in which the stimuli to other major reflexogenic areas were controlled and the lung was shown to possess reflex activity. Dogs were anaesthetised with -chloralose, artificially ventilated, the chests widely opened and a cardiopulmonary bypass established. The intrapulmonary region of the left lung was isolated and perfused through the left pulmonary artery and drained through cannulae in the left pulmonary veins via a Starling resistance. Intrapulmonary arterial and venous pressures were controlled by the rate of inflow of blood and the pressure applied to the Starling resistance. Pressures to the carotid, aortic and coronary baroreceptors and heart chambers were controlled. Responses of vascular resistance were assessed from changes in perfusion pressures to a vascularly isolated hind limb and to the remainder of the subdiaphragmatic circulation (flows constant). The reactivity of the preparation was demonstrated by observing decreases in vascular resistance to large step changes in carotid sinus pressure (systemic vascular resistance decreased by -40 +/- 5%), chemical stimulation of lung receptors by injection into the pulmonary circulation of veratridine or capsaicin (resistance decreased by -32 +/- 4%) and, in the four dogs tested, increasing pulmonary stroke volume to 450 ml (resistance decreased by -24 +/- 6%). However, despite this evidence that the lung was innervated, increases in intrapulmonary arterial pressure from 14 +/- 1 to 43 +/- 3 mmHg or in intrapulmonary venous pressure from 5 +/- 2 to 34 +/- 2 mmHg or both did not result in any consistent changes in systemic or limb vascular resistances. In two animals tested, however, there were marked decreases in efferent phrenic nerve activity. These results indicate that increases in pressure confined to the intrapulmonary arterial and venous circulations do not cause consistent reflex vascular responses, even though the preparation was shown to be reflexly active and the lung was shown to be innervated.     

Pressure/flow relation in the peripheral pulmonary vascular bed in dogs: a preliminary study.

In order to test a technique for the determination of the pressure/flow relationship in the peripheral pulmonary vascular bed, the perfusion pressure changes with increasing and then decreasing flow in a small part of the lung (around 1 ml) were studied in anaesthetized supine dogs, after insertion of a specially designed double distal lumen Swan-Ganz catheter. One lumen was used for the pressure measurement, one for infusion of saline by a pump with variable flow, from 0.1 to 1.0 ml s-1. A conventional thermodilution Swan-Ganz catheter was also advanced in the pulmonary artery, to measure pressures in the pulmonary circulation as well as cardiac output. During infusion in the wedged catheter, right atrial, pulmonary arterial and balloon occlusion wedge pressures did not change. The pressure/flow curve of the occluded vascular bed showed a shape similar to that of collapsible tubes, with a pressure plateau at high flow, but this could also be due to vascular recruitment. The curve exhibited hysteresis, with a lower pressure when flow decreased. The slope of the initial part of the curve increased, on average, from 54 +/- 9 during normoxia to 91 +/- 27 mmHg s ml-1 during hypoxia (FIO2 = 0.10); this difference was not significant, but the perfusion pressure at high flow was significantly higher during hypoxia (P less than 0.05). Using blood instead of saline would allow the determination of the peripheral pulmonary vascular resistance under physiological conditions, and further work is needed to estimate the sensitivity and the reproducibility of this technique.     

The vasomotor component of the carotid sinus baroreceptor reflex in the cat during stimulation of the hypothalamic defence area

1. The effect of moderate intensities of stimulation of the hypothalamic defence area on the baroreceptor reflex has been investigated in the cat by comparing the responses of arterial blood pressure and perfusion pressure of the isolated hind-limb muscle bed perfused at constant volume inflow, when the isolated carotid sinus was subjected to a series of non-pulsatile pressures with and without simultaneous hypothalamic stimulation.2. In the absence of hypothalamic stimulation the characteristic sigmoid curves relating sinus pressure to blood pressure or muscle perfusion pressure were obtained.3. With simultaneous stimulation of the hypothalamus a similar sigmoid relationship was found. There was no evidence of any reduction in the over-all power or maximum sensitivity of the baroreceptor reflex.4. However, in those cats which had been atropinized to abolish the cholinergically mediated muscle vasodilatation, the curves obtained during hypothalamic stimulation were displaced in such a manner as to suggest that, while baroreceptor modulation of vasoconstrictor tone continued during defence area stimulation, the blood pressure regulating mechanism had been ;reset' so that, within the physiological range of sinus pressures, any given level of sinus pressure was associated with a greater vasoconstrictor tone.5. In non-atropinized cats there was little displacement of the curves relating sinus pressure to blood pressure, while the curves relating sinus pressure to muscle perfusion pressure were displaced in the opposite direction so that over-all muscle vascular resistance was less than normal at each level of sinus pressure.     

Comparison of the reflex vasomotor responses to separate and combined stimulation of the carotid sinus and aortic arch baroreceptors by pulsatile and non-pulsatile pressures in 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. When the vasosensory areas were perfused at non-pulsatile pressures within the normal physiological range of mean pressures, the reflex reduction in systemic vascular resistance produced by a given rise in mean carotid sinus pressure was significantly greater than that resulting from the same rise of aortic arch pressure.3. On the other hand, when the vasosensory areas were perfused at normal pulsatile pressures and within the normal physiological range of mean pressures, there was no difference in the size of the reflex vascular responses elicited by the same rise in mean pressure in the carotid sinuses and in the aortic arch.4. Whereas the vasomotor responses elicited reflexly by changes in mean carotid sinus pressure are modified by alterations in pulse pressure, those evoked by the aortic arch baroreceptors through changes of mean pressure are only weakly affected by modifications in pulse pressure. Evidence for this was obtained from single stepwise changes of mean pressure in each vasosensory area during pulsatile and non-pulsatile perfusion, and from curves relating the mean pressure in the carotid sinuses or aortic arch and systemic arterial perfusion pressure.5. The vasomotor response elicited by combined stimulation of the carotid sinus and aortic arch baroreceptors was greater than either response resulting from their separate stimulation.6. When the mean perfusion pressures in the two vasosensory areas are changed together, the curve relating mean pressure to systemic arterial pressure during pulsatile perfusion of the areas is considerably flatter than that for non-pulsatile perfusion.7. Increasing the pulse pressure in the carotid sinuses or aortic arch caused a decrease in systemic vascular resistance, the response elicited from the carotid sinuses being the larger.8. Altering the phase angle between the pulse pressure waves in the carotid sinuses and aortic arch had no effect on systemic vascular resistance.9. In both vasosensory areas, increasing the pulse frequency caused a reduction in systemic vascular resistance.     

Pressure/flow relation in the peripheral pulmonary vascular bed in dogs: a preliminary study

In order to test a technique for the determination of the pressure/flow relationship in the peripheral pulmonary vascular bed, the perfusion pressure changes with increasing and then decreasing flow in a small part of the lung (around 1 ml) were studied in anaesthetized supine dogs, after insertion of a specially designed double distal lumen Swan–Ganz catheter. One lumen was used for the pressure measurement, one for infusion of saline by a pump with variable flow, from 0.1 to 1.0 ml s^-1. A conventional thermodilution Swan–Ganz catheter was also advanced in the pulmonary artery, to measure pressures in the pulmonary circulation as well as cardiac output. During infusion in the wedged catheter, right atrial, pulmonary arterial and balloon occlusion wedge pressures did not change. The pressure/flow curve of the occluded vascular bed showed a shape similar to that of collapsible tubes, with a pressure plateau at high flow, but this could also be due to vascular recruitment. The curve exhibited hysteresis, with a lower pressure when flow decreased. The slope of the initial part of the curve increased, on average, from 54±9 during normoxia to 91±27 mmHg s ml^-1during hypoxia (FIO₂= 0.10); this difference was not significant, but the perfusion pressure at high flow was significantly higher during hypoxia (P < 0.05). Using blood instead of saline would allow the determination of the peripheral pulmonary vascular resistance under physiological conditions, and further work is needed to estimate the sensitivity and the reproducibility of this technique.     

Determinants of systemic zero-flow arterial pressure

Thirteen pentobarbital-anesthetized dogs whose carotid sinuses were isolated and perfused at a constant pressure were placed on total cardiac bypass. With systemic venous pressure held at 0 mmHg (condition 1), arterial inflow was stopped for 20 s at intrasinus pressures of 50, 125, and 200 mmHg. Zero-flow arterial pressures under condition 1 were 16.2 +/- 1.3 (SE), 13.8 +/- 1.1, and 12.5 +/- 0.8 mmHg, respectively. In condition 2, the venous outflow tube was clamped at the instant of stopping the inflow, causing venous pressure to rise. The zero-flow arterial pressures were 19.7 +/- 1.3, 18.5 +/- 1.4, and 16.4 +/- 1.2 mmHg for intrasinus pressures of 50, 125, and 200 mmHg, respectively. At all levels of intrasinus pressure, the zero-flow arterial pressure in condition 2 was higher (P less than 0.005) than in condition 1. In seven dogs, at an intrasinus pressure of 125 mmHg, epinephrine increased the zero-flow arterial pressure by 3.0 mmHg, whereas hexamethonium and papaverine decreased the zero-flow arterial pressure by 2 mmHg. Reductions in the hematocrit from 52 to 11% resulted in statistically significant changes (P less than 0.01) in zero-flow arterial pressures. Thus zero-flow arterial pressure was found to be affected by changes in venous pressure, hematocrit, and vasomotor tone. The evidence does not support the literally interpreted concept of the vascular waterfall as the model for the finite arteriovenous pressure difference at zero flow.     

Reflex vascular responses to changes in left ventricular pressures, heart rate and inotropic state in dogs.

Dogs were anaesthetized with chloralose, artificially ventilated and the chests widely opened. Left ventricular mechanoreceptors, including those in or near the coronary arteries, were stimulated by changing the pressure in the aortic root. The pressures distending the left atrium and the aortic and carotid baroreceptors were controlled. Reflex vascular responses were assessed from changes in perfusion pressures to a hind limb and to the rest of the systemic circulation, which were perfused independently at constant flows. Physiological increases in peak left ventricular and coronary arterial pressures resulted in vasodilatation in both regions. These responses were not influenced by changes in the heart rate. Stimulation of the left cardiac sympathetic nerves resulted in increases in peak ventricular pressure and in the maximal rate of change of pressure (dP/dtmax). This also resulted in increases in perfusion pressures (vasoconstriction) at all levels of peak ventricular pressure although there was little effect on the responses to changes in ventricular pressure. Sympathetic stimulation had little effect on the relationship between perfusion pressures and aortic root pressure. Increases in ventricular filling also resulted in vasoconstriction at all levels of peak ventricular pressure. Increases in filling, however, did not affect the relationship between either perfusion pressure and aortic root pressure. Conversely, decreases in left ventricular filling, by bypassing some of the left atrial blood, resulted in vasodilatation at all levels of peak ventricular pressures but had no effect on the perfusion pressures at any aortic root pressure. The combination of sympathetic stimulation with decreased ventricular filling resulted in little effect on perfusion pressures or on their responses to changes in either aortic root or ventricular systolic pressures. We conclude that the vascular responses to stimulation of left ventricular mechanoreceptors are not enhanced by sympathetic stimulation, decreases in ventricular filling or the combination of the two. The apparent effects of each of these interventions alone on the relationships between perfusion pressures and ventricular, but not aortic root, pressure, could be explained if the receptors responsible were sensitive more to changes in aortic root and coronary arterial pressures than to pressure changes in the ventricle itself.     

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.     

Hypoxia and pulmonary arterial pressure in the rabbit

1. The effect of hypoxia on pulmonary arterial pressure was studied in young and adult rabbits.2. In isolated perfused lungs, hypoxia caused no rise in pulmonary arterial pressure in rabbits on the day of birth. The size of the hypoxic response increased progressively until 9-11 days of age, when the adult response of a 20% rise of pulmonary arterial pressure at constant flow was attained.3. The intact adult rabbit responded to hypoxia with a 14-30% rise in pulmonary arterial pressure, attributed to vasoconstriction and independent of frequency or tidal volume during positive pressure ventilation.     

Zur Lokalisation der autoregulativen Widerstandsänderungen in der Niere

Summary Micropuncture studies of pressures within tubules and peritubular capillaries in the rat kidney have been carried out with variable arterial pressures within the autoregulation range.These pressures both have been found to be virtually constant on both structures when the arterial pressure was varied.After paralyzing the vascular smooth muscles by intravenous injection of papaverin, the tubular as well as the peritubular capillary pressures went up when the arterial pressure was increased.The data indicate that the resistance to flow in the kidney, which varies with arterial pressure, is located in the preglomerular vascular bed and depends on the integrity of the vascular smooth muscle. The results contradict those theories which state that the increase in resistance to flow during elevated arterial pressure is caused by an increased tissue pressure compressing the vascular channels.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft. Herrn Professor H. Wirz, in dessen Laboratorium ein Teil der Versuche ausgeführt wurde, sind wir für seine Ratschläge bei der Abfassung des Manuskriptes zu großem Dank verpflichtet.     

The role of cardiac sympathetic discharges during the pulmonary depressor reflex.

The role played by the cardiac sympathetic fibers in the pulmonary depressor reflex was analyzed in twenty dogs. The selective perfusion with homologous blood of the inferior lobar vessels of the left lung with pressures of 40 to 60 mmHg decreased the spontaneous background discharges recorded from the left superior or inferior cardiac sympathetic nerves. This decrease was maximal at perfusion pressure of 80-100 mmHg. Following the decrease in the sympathetic discharges, the systolic and diastolic systemic arterial blood pressure decrease about 10 per cent. The changes were reversible when the perfusion pressure was returned to the control. The intravenous injection of atropine sulphate did not change either the systemic hypotension or the responses of the sympathetic efferent discharges induced by elevation of the pressure in the vascular bed of the lung lobe. Thus, it is believed that the systemic arterial blood pressure during this reflex may have fallen due to a diminution of the vascular tone caused by a decrease in the sympathetic efferent discharges. After transection of the vagus nerve ipsilateral to the tested lobe, the reduction of the sympathetic discharges as well as the decrease of the systemic arterial blood pressure were no longer observed. Our results further substantiate the concept that the vagus nerve is the afferent pathway for the pulmonary depressor reflex, and it may be concluded that during this reflex the sympathetic efferent activities are inhibited.     

Coronary vascular and myocardial responses to carotid body stimulation in the dog.

Coronary vascular and myocardial responses to selective hypoxic and/or hypercapnic carotid chemoreceptor stimulation were investigated in constantly ventilated, pentobarbital or urethan-chloralose anesthetized dogs. Bilaterally isolated carotid chemoreceptors were perfused with autologous blood of varying O2 and CO2 tensions via an extracorporeal lung circuit. Systemic gas tensions were unchanged. Effects of carotid chemoreceptor stimulation on coronary vascular resistance, left ventricular dP/dt, and strain-gauge arch output were studied at natural coronary blood flow with the chest closed and during constant-flow perfusion of the left common coronary artery with the chest open. Carotid chemoreceptor stimulation slightly increased left ventricular dP/dt and slightly decreased the strain-gauge arch output, while markedly increasing systemic pressure. Coronary blood flow increased; however, coronary vascular resistance wa.as not affected. These studies show that local carotid body stimulation increases coronary blood flow but has little effect on the myocardium. The increase in coronary blood flow results mainly from an increase in systemic arterial pressure. Thus these data provide little evidence for increased sympathetic activity of the heart during local stimulation of the carotid chemoreceptors with hypoxic and hypercapnic blood.     

Influence of carotid baroreceptors on different components of the vascular system

1. Reflex changes in wall tension of the lateral saphenous vein of one hind limb, the splenic veins and capsule, and the resistance vessels of the other hind limb caused by changes in baroreceptor activity were measured in vagotomized dogs under thiopentone-chloralose anaesthesia.2. Three different methods were used to alter pressure in one or both carotid sinuses. (1) Both carotid sinuses were vascularly isolated and filled with fully oxygenated Krebs-Ringer bicarbonate solution (pH 7.4) from a reservoir in which the pressure could be altered at will. (2) One sinus was denervated, and the contralateral sinus was perfused with arterial blood at different flow rates. (3) One sinus was denervated, and the innervated sinus was perfused with arterial blood at constant flow, the pressure being altered by changing the outflow resistance.3. The left saphenous vein was perfused at constant flow with autologous blood; changes in perfusion pressure were used as a measure of changes in veno-motor activity. The right common iliac artery was perfused at constant flow to measure changes in resistance vessel activity. Blood flow through the spleen was temporarily arrested, trapping a fixed volume of blood in the organ. Under these conditions, changes in splenic vein pressure were a measure of changes in smooth-muscle tension in the splenic capsule and veins.4. In order to assess the responses to baroreceptor stimulation in terms of alterations in sympathetic nerve traffic to different components of the peripheral vascular system, ;frequency-response curves' were constructed for spleen, saphenous vein, and limb resistance vessels by electrical stimulation of the splenic nerves and lumbar sympathetic chains.5. The saphenous vein showed no consistent response to changes in baroreceptor activity. Reduction in carotid sinus pressure from 180 to 100 mm Hg caused an increase in venous pressure in the isovolumetric spleen and in the iliac artery perfusion pressure. These results were confirmed by electrical stimulation of the carotid sinus nerve. Whereas the peak responses of the limb resistance vessels corresponded to an increase in lumbar sympathetic nerve traffic of 6-10 c/s, the maximal splenic responses were equivalent to an increase in splenic nerve traffic of 1-4 c/s. These results are consistent with selective autonomic nervous control of different components of the peripheral vascular system.     

Inhibition of nitric oxide synthesis potentiates hypoxic vasoconstriction in isolated rat lungs

We have investigated the influence of endogenous nitric oxide (NO) on the vascular resistance of isolated rat lungs by inhibiting its synthesis with the false substrate N-monomethyl-L-arginine (L-NMMA). When perfused with blood at constant flow the addition of L-NMMA (10(-3) M) did not affect pulmonary arterial pressure in hyperoxia but did increase the response to hypoxia (PO2 25-35 mmHg) by 2.5 +/- 0.2 fold (mean +/- S.E.M.). The effect of L-NMMA was reversed by 3 x 10(-3) M-L-arginine, the true substrate for NO synthesis. Thus NO is an important pulmonary vasodilator but hypoxic vasoconstriction does not result from a reduction of its background release.     

Rapid intravenous infusion of 20 mL/kg saline alters the distribution of perfusion in healthy supine humans

Rapid intravenous saline infusion, a model meant to replicate the initial changes leading to pulmonary interstitial edema, increases pulmonary arterial pressure in humans. We hypothesized that this would alter lung perfusion distribution. Six healthy subjects (29 ± 6 years) underwent magnetic resonance imaging to quantify perfusion using arterial spin labeling. Regional proton density was measured using a fast-gradient echo sequence, allowing blood delivered to the slice to be normalized for density and quantified in mL/min/g. Contributions from flow in large conduit vessels were minimized using a flow cutoff value (blood delivered > 35% maximum in mL/min/cm(3)) in order to obtain an estimate of blood delivered to the capillary bed (perfusion). Images were acquired supine at baseline, after infusion of 20 mL/kg saline, and after a short upright recovery period for a single sagittal slice in the right lung during breath-holds at functional residual capacity. Thoracic fluid content measured by impedance cardiography was elevated post-infusion by up to 13% (p<0.0001). Forced expiratory volume in 1s was reduced by 5.1% post-20 mL/kg (p=0.007). Infusion increased perfusion in nondependent lung by up to 16% (6.4 ± 1.6 mL/min/g baseline, 7.3 ± 1.8 post, 7.4 ± 1.7 recovery, p=0.03). Including conduit vessels, blood delivered in dependent lung was unchanged post-infusion; however, was increased at recovery (9.4 ± 2.7 mL/min/g baseline, 9.7 ± 2.0 post, 11.3 ± 2.2 recovery, p=0.01). After accounting for changes in conduit vessels, there were no significant changes in perfusion in dependent lung following infusion (7.8 ± 1.9 mL/min/g baseline, 7.9 ± 2.0 post, 8.5 ± 2.1 recovery, p=0.36). There were no significant changes in lung density. These data suggest that saline infusion increased perfusion to nondependent lung, consistent with an increase in intravascular pressures. Dependent lung may have been "protected" from increases in perfusion following infusion due to gravitational compression of the pulmonary vasculature.     

Glucagon inhibition of hepatic arterial responses to hepatic nerve stimulation

The hepatic arterial vascular bed of the chloaralose-urethan-anesthetized dog was perfused with blood from a cannulated femoral artery. Hepatic arterial blood flow and perfusion pressure were measured. The hepatic periarterial postganglionic sympathetic nerves were stimulated supramaximally at 0.1, 0.5, 1, 2, 5, 10, and 20 Hz; this caused frequency-dependent rises in the calculated hepatic arterial vascular resistance at all frequencies above the threshold of 0.1 or 0.5 Hz. Glucagon was infused intra-arterially in dosese from 0.25 to 10 microgram/min; glucagon antagonized both the vasoconstrictor effects of hepatic nerve stimulation and of intra-arterial injections of norepinephrine. The degree of antagonism of these responses was significantly correlated with the calculated hepatic arterial glucagon concentration. It is possible that glucagon released physiologically in stress and hypoglycemia may protect the hepatic arterial vasculature from the effects of increased sympathetic discharge.