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.     

5-Hydroxytryptamine-induced microvascular pressure transients in lungs of anaesthetized rabbits.

We determined lung microvascular pressure transients induced by 5-hydroxytryptamine (5HT), by the micropuncture technique. We mechanically ventilated anaesthetized (halothane 0.8%), open-chested rabbits, in which we recorded pulmonary artery (PA), left atrial (LA) and carotid artery pressures and cardiac output. For 4-min periods of stopped ventilation, we constantly inflated the lung with airway pressure of 7 cmH2O, then micropunctured the lung to determine pressures in arterioles and venules of 20-25 microm diameter. An intravenous bolus infusion of 5HT (100 microg), increased total pulmonary vascular resistance by 59%. Prior to 5HT infusion, the arterial, microvascular and venous segments comprised 30, 50 and 19% of the total pulmonary vascular pressure drop, respectively. However 14 s after 5HT infusion, the PA-arteriole pressure difference (arterial pressure drop) increased 46%, while the venule-LA pressure difference (venous pressure drop) increased >100%. The arteriole-venule pressure difference (microvascular pressure drop) was abolished. The increase in the arterial pressure drop was maintained for 4.8 min, whereas the increased venous pressure drop reverted to baseline in <1 min. We conclude that in the rabbit lung in situ, a 5HT bolus causes sustained arterial constriction and a strong but transient venous constriction.     

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.     

Atrial natriuretic peptide attenuates an increase in pulmonary vascular incremental resistance due to high pulmonary venous pressure.

The aim of this study was to determine whether an elevation of pulmonary venous pressure (PVP) and atrial natriuretic peptide (ANP) affects pulmonary vascular resistance (PVR) and pulmonary vascular incremental resistance (iPVR). We vascularly isolated the left lower lobe of the lung and perfused it with blood using a pulsatile pump. Blood flow (PBF) to the isolated lobe was decreased in 6 to 7 steps from about 8 to 1 ml/(kg.min). PVR was calculated from measurements of PBF and the pressure difference between pulmonary arterial pressure and PVP at four different levels of fixed PVP. iPVR was estimated from a slope of the pressure-flow relationships between effective pulmonary driving pressure and PBF at four different levels of fixed PVP. iPVR was 2.2 +/- 0.2, 2.2 +/- 0.1, 2.4 +/- 0.1, and 2.6 +/- 0.2 mmHg.min.kg/ml, when PVP was 0, 5, 10, and 15 mmHg, respectively. To test whether or not the response of the pulmonary vascular bed to the elevated PVP is modulated by ANP, iPVR was estimated before and after an administration of ANP in the perfusion circuit. Increased iPVR from 2.1 +/- 0.2 to 2.5 +/- 0.2 mmHg.min.kg/ml in response to the elevation of PVP from 0 to 15 mmHg decreased to the control level after the administration of ANP. ANP, however, did not change the control iPVR. PVR decreased with increasing PVP. ANP decreased PVR when PVP was 0 mmHg, but did not change it when PVP was 15 mmHg. These results suggest that ANP decreases PVR and restores the decreased pulmonary vascular compliance.     

Pulmonary vasoconstriction in asphyxia during cross-circulation between twin foetal lambs

1. The effect of asphyxia on pulmonary vascular resistance was measured in anaesthetized foetal lambs whose left lung was supplied with arterial blood from a twin, both still being attached to their placentas by intact umbilical cords.2. In foetal lambs of 91-92 days gestation asphyxia of the recipient caused no pulmonary vasoconstriction so long as its left pulmonary artery was supplied with normal blood from a twin donor. Asphyxia of the donor caused pulmonary vasoconstriction in the unasphyxiated recipient; this was therefore wholly due to a local effect of the blood passing through the lung.3. In foetal lambs of 98-142 days gestation asphyxia of the recipient caused a small degree of pulmonary vasoconstriction, even though the left pulmonary artery was supplied with normal blood from the twin donor. This vasoconstriction was abolished by administration of hexamethonium or by cutting the sympathetic nerves to the left lung.4. In mature foetal lambs pulmonary arterial inflow and venous outflow were measured simultaneously. Broncho-pulmonary blood flow was less than 5% of total pulmonary flow. Pulmonary O(2) consumption was 0.75 +/- 0.11 ml./100 g.min, or about 5% of total foetal O(2) consumption.     

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.     

Effects of venous pressure elevation on myogenic vasoconstrictive responses to static and dynamic arterial pressures

In order to establish the nature of the stretch-evoked dynamic properties of vascular smooth muscle in arterioles, we have examined the static and dynamic effects of both arterial pulse pressure and elevated venous pressure on the resistance vessels (arteries and arterioles) in an intestinal mesenteric preparation derived from dogs. The dynamic myogenic response to stretch stimuli was directly related to both the frequency of arterial pulse pressure (1-20 c/min) and the level of venous pressure (0-45 mmHg). Under elevated venous pressure (20 mmHg), the mean arterial flow decreased with an increase in the frequency of arterial pulse pressure. The arteriolar vascular tone (namely, vascular resistance) was seen to be enhanced. We found that elevated venous pressure promotes active constriction (9-53%) of arteriolar smooth muscle (myogenic mechanism). The elevation of venous pressure also caused a rhythmic constriction (vasomotion) in the site of both vein and artery, which was completely abolished by an alpha-blocker (phentolamine). The results suggest that during venous pressure elevation a very pronounced myogenic constriction in terminal arterioles is caused by either a local neural reflex or a propagated myogenic response in the arteriolar network.     

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.     

Carotid baroreceptor reflexes in humans during orthostatic stress

Orthostatic stress, including standing, head-up tilting and lower body suction, results in increases in peripheral vascular resistance but little or no change in mean arterial pressure. This study was undertaken to determine whether the sensitivity of the carotid baroreceptor reflex was enhanced during conditions of decreased venous return. We studied eight healthy subjects and determined responses of pulse interval (ECG) and forearm vascular resistance (mean finger blood pressure divided by Doppler estimate of brachial artery blood velocity) to graded increases and decreases in carotid transmural pressure, effected by a neck suction/pressure device. Responses were determined with and without the application of lower body negative pressure (LBNP) at -40 mmHg. Stimulus-response curves were determined as the responses to graded neck pressure changes and the differential of this provided estimates of reflex sensitivity. Changes in carotid transmural pressure caused graded changes in R-R interval and vascular resistance. The cardiac responses were unaffected by LBNP. Vascular resistance responses, however, were significantly enhanced during LBNP and the peak gain of the reflex was increased from 1.2 +/- 0.3 (mean +/- S.E.M.) to 2.2 +/- 0.3 units (P < 0.05). The increased baroreflex gain may contribute to maintenance of blood pressure during orthostatic stress and limit the pressure decreases during prolonged periods of such stress.     

Pulmonary and systemic vascular responses of perinatal goats to prostaglandins E1 and E2.

Effects of prostaglandins of the E series and their metabolites on pulmonary and systemic circulations of newborn and exteriorized fetal goats (anesthetized with chloralose) were evaluated in situ using an isolated perfused left lung lobe preparation. Prostaglandin E1 (PGE1) and, to a lesser extent, prostaglandin E2 (PGE2) infusions resulted in decreases of pulmonary vascular resistance (PVR) of fetal and neonatal goats. Infusions of PGE1 or PGE2 (less than 2 microgram.kg-1.min-1 for 1 min) directly into left pulmonary arterial blood did not affect systemic arterial pressure (SAP). Infusions of PGEs (greater than 2 microgram.kg-1.min-1 for 1 min) resulted in decreases in SAP and heart rate. The dose-response characteristics of the pulmonary circulation in response to PGE1 and PGE2 were not different in fetal and newborn goats. Fetal asphyxia did not alter the dose-response characteristics of pulmonary circulation in response to PGE1. Metabolites (15-keto) of PGE1 and PGE2 had no effect upon PVR or SAP of perinatal goats. These results demonstrate in perinatal mammals 1) vasodilator action of PGE1 and PGE2 on the pulmonary and systemic circulations, and 2) catabolism by the lungs of these prostaglandins.     

5‐Hydroxytryptamine‐induced microvascular pressure transients in lungs of anaesthetized rabbits

We determined lung microvascular pressure transients induced by 5‐hydroxytryptamine (5HT), by the micropuncture technique. We mechanically ventilated anaesthetized (halothane 0.8%), open‐chested rabbits, in which we recorded pulmonary artery (PA), left atrial (LA) and carotid artery pressures and cardiac output. For 4‐min periods of stopped ventilation, we constantly inflated the lung with airway pressure of 7 cmH₂O, then micropunctured the lung to determine pressures in arterioles and venules of 20–25 μm diameter. An intravenous bolus infusion of 5HT (100 μg), increased total pulmonary vascular resistance by 59%. Prior to 5HT infusion, the arterial, microvascular and venous segments comprised 30, 50 and 19% of the total pulmonary vascular pressure drop, respectively. However 14 s after 5HT infusion, the PA‐arteriole pressure difference (arterial pressure drop) increased 46%, while the venule‐LA pressure difference (venous pressure drop) increased >100%. The arteriole–venule pressure difference (microvascular pressure drop) was abolished. The increase in the arterial pressure drop was maintained for 4.8 min, whereas the increased venous pressure drop reverted to baseline in <1 min. We conclude that in the rabbit lung in situ, a 5HT bolus causes sustained arterial constriction and a strong but transient venous constriction.     

Endogenous nitric oxide as a probable modulator of pulmonary circulation and hypoxic pressor response in vivo.

The objective of this study was to investigate the role of endogenous nitric oxide, formed from L-arginine, in the regulation of pulmonary circulation in vivo, with special reference to the hypoxic pressor response. In artificially ventilated open-chest rabbits, pulmonary vascular resistance at normoxic ventilation (FIO2 = 21%) was 78 +/- 16 cmH2O ml-1 min 1000-1 (mRUL). Hypoxic ventilation (FIO2 = 10%) increased pulmonary vascular resistance to 117 +/- 17 mRUL. N omega-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, increased pulmonary vascular resistance at normoxic ventilation to 192 +/- 28 mRUL and during hypoxic ventilation to 462 +/- 80 mRUL. During N omega-nitro-L-arginine methylester infusion there was also an increase in mean arterial blood pressure as well as a decrease in cardiac output that was even more pronounced during hypoxic ventilation. L-arginine reversed the effect of N omega-nitro-L-arginine methylester on pulmonary vascular resistance at normoxic ventilation to 140 +/- 26 mRUL and at hypoxic ventilation to 239 +/- 42 mRUL. In spontaneously breathing closed-chest rabbits, N omega-nitro-L-arginine methylester evoked a marked decrease in arterial PO2 and increases in respiration frequency and central venous pressure, while blood pH, PCO2 and base excess remained unchanged. Taken together these findings indicate that endogenous nitric oxide, formed from L-arginine, might be a regulator of ventilation-perfusion matching at normoxic ventilation, and that nitric oxide acts as an endogenous modulator of the hypoxic pressor response.     

The role of adrenergic receptor blockade in serotonin-induced changes in the pulmonary circulation.

1. In dogs i.v. injection of serotonin caused a rise in pulmonary artery pressure and pulmonary arteriocapillary resistance that persisted even after alpha- and beta-adrenergic receptor blockade; pulmonary venous resistance also increased, but this was abolished by pretreatment with either propranolol or phenoxybenzamine. 2. The injection of serotonin into the ascending aorta produced an immediate rise in systemic, pulmonary arterial and pulmonary venous pressures and pulmonary venous resistance. After phenoxybenzmine, the rise in systemic and pulmonary arterial pressures remained unchanged, but previously observed increases in pulmonary venous pressure and resistance were blocked. In contrast, propranolol failed to abolish the rise in pulmonary venous resistance after serotonin injection into the ascending aorta. 3. These results confirm the observation that the vasoconstrictor effect attributed to intravenously injected serotonin on the arterial side of the pulmonary circulation is independent of the known sympathetic pathways. The data suggest that the pulmonary venoconstriction induced by intravenous serotonin is of reflex origin, abolished by alpha and beta receptor blockade, whereas the efferent arm of the reflex pulmonary venoconstriction following injection of serotonin into the ascending aorta is mediated via alpha-adrenergic receptors.     

Pulmonary vascular disease and hypertension after valve surgery for mitral stenosis

The reduction of pulmonary hypertension that occurs within 24 hours of valve replacement for mitral stenosis is well documented, but patients who die after surgery have not been adequately studied. Clinical and autopsy data for 16 patients who died following mitral valve replacement were reviewed. The emphasis was on preoperative and postoperative pulmonary arterial pressure and pulmonary vascular disease, including arterial, venous, and capillary changes. Morphologic features were graded and summed to obtain an additive histologic assessment (AHA). Patients were divided into three groups: 1) those who had uneventful operations and early postoperative periods but died prior to discharge; 2) those who had postoperative difficulty, with identifiable acute anatomic causes of death; and 3) those who had postoperative difficulty, with no apparent acute anatomic cause of death. In group 1 (n = 4) the preoperative pulmonary arterial pressure was 43 +/- 17 mm Hg, and AHA ranged from 0 to 4; in group 2 (n = 5) the preoperative pulmonary arterial pressure was 60 +/- 15 mm Hg, but AHA ranged only from 2 to 5. In group 3 (n = 7) the preoperative pulmonary arterial pressure was 59 +/- 12 mm Hg; AHA ranged from 6 to 9, significantly higher than that of the other groups (P less than 0.005). Three patients from group 3 had elevated pulmonary arterial pressure (60, 52, and 50 mm Hg three, six, and 15 days after surgery, respectively). Two additional patients had right heart failure with normally contracting left ventricles terminally. It is concluded that some patients with mitral stenosis who die after surgery with persistently elevated pulmonary arterial pressure have sufficiently severe pulmonary vascular disease to account for their persistent pulmonary hypertension and death.     

Continuous air embolization into sheep causes sustained pulmonary hypertension and increased pulmonary vasoreactivity.

Baseline pulmonary arterial, left atrial and systemic artery pressures, cardiac output, and lung lymph flow were measured in seven chronically catheterized sheep before continuous air embolization into the pulmonary artery, which caused a two-to-threefold increase in pulmonary vascular resistance (PVR) for 12 days. Air embolization was discontinued on days 4, 8, and 12 and hemodynamic measurements were repeated. Thromboxane B2, 6-keto-PGF1 alpha, and protein were measured in lung lymph and blood plasma on days 0, 4, 8 and 12. Air embolization caused an acute, sustained rise in pulmonary artery pressure and PVR (baseline, 3.68 +/- 0.21; air, 8.32 +/- 0.62, mean +/- SE). By day 4, PVR was increased significantly even when air flow was interrupted (5.97 +/- 0.72) and by day 12, it was almost twice baseline; pulmonary artery pressure also remained elevated (baseline, 19 +/- 1 cm H2O; day 12, 31 +/- 3). Pulmonary vasoreactivity to PGH2-A was significantly increased on days 4, 8, and 12 (day 12, 285 +/- 41% of baseline response). Lung lymph flow, protein, and thromboxane clearance were increased throughout the study while clearance of 6-keto-PGF1 alpha was increased at day 4 and falling by day 8. At autopsy, morphometric analysis of the barium-injected pulmonary arterial bed revealed striking structural remodeling, extension of muscle into smaller arteries than normal: decreased peripheral arterial filling, increased medial thickness, and dilated large pulmonary arteries. Continuous air embolization into sheep causes the structural and functional changes of chronic pulmonary hypertension accompanied by increased pulmonary vasoreactivity to a bolus of PGH2-A. The abrupt onset of the sustained elevation in PVR induced by air embolization may account for the severity of the structural remodelling, particularly for the increased medial thickness.     

Peripheral blood flows during colorectal distension in anaesthetised dogs

Distension of the descending colon elicits reflex cardiovascular responses, including increases in heart rate and arterial blood pressure. To study the relative contribution of vasoconstriction in individual vascular beds to this reflex response, experiments were performed on seven dogs anaesthetised with chloralose and instrumented with electromagnetic flowmeters around the superior mesenteric, the left renal and the left external iliac arteries. The colorectal portion of the intestine was distended at constant pressure (36.6 mm Hg, 4.9 kPa mean; range 25–50 mm Hg, 3.3–6.7 kPa) with warm Ringer solution for periods of 2 min. After a set of control distensions, the experiments were performed whilst the reflex rise in arterial pressure was prevented by removal of blood from the arterial tree. In control distensions arterial pressure increased by 11.3±1.5 mm Hg, 1.51±0.12 kPa (mean±SEM). In distensions at constant arterial pressure, peripheral blood flows were altered to different extents in the three territories studied: vascular resistance increased by 30.8±5.6% (P<0.01) in the mesenteric, by 4.1±1.5% (P<0.03) in the renal, and by 15.2±6.8% (NS) in the external iliac bed. We conclude that colorectal distension may reflect activation of a function-specific pathway of the sympathetic nervous system, which leads to much greater vasoconstriction in the splanchnic circulation than in renal or musculocutaneous circulations.     

Influence of inhibitors of prostaglandin synthesis on the canine pulmonary vascular bed.

The effects of two chemically dissimilar inhibitors of prostaglandin (PG) synthesis on vascular resistance and responses to pressor and depressor hormones were evaluated in the canine pulmonary vascular bed. Indomethacin or meclofenamate, 2.5-5 mg/kg iv, increased lobar arterial pressure. Since lobar blood flow was held constant and left atrial pressure did not change, the rise in pressure reflects an increase in vascular resistance. The rise in lobar pressure after indomethacin occurred in the absence of a change in lobar venous or translobar airway pressure. This agent enhanced the response to angiotensin but not to norepinephrine. Meclofenamate decreased responses to both agents. Indomethacin enhanced the dilator response to PGE1 and both indomethacin and meclofenamate increased the response to PGF2alpha. These data indicate that the rise in resistance after indomethacin or meclofenamate was the result of vasoconstriction in vessels upstream to the small veins, presumed to be small arteries. These data are consistent with the hypothesis that under resting conditions synthesis of a dilator prostaglandin may be important for the maintenance of the pulmonary vascular bed in a dilated state. However, results of the present study are not consistent with the postulate that prostaglandins modulate responses to norepinephrine but suggest that indomethacin and meclofenamate interfere with the inactivation of PGF2alpha and PGE1 in the lung.     

Sympathoadrenal mechanisms in hemodynamic responses to gastric distension in cats

There is presently little information on the efferent mechanisms responsible for the reflex cardiovascular activation during passive gastric distension. Therefore, 40 cats anesthetized with alpha-chloralose were studied with passive gastric balloon distention before and during 1) two repeated gastric distensions, 2) beta-adrenergic blockade with propranolol, 3) alpha-adrenergic blockade with phentolamine, or 4) bilateral adrenalectomy. Before and during each distension mean arterial pressure, heart rate, cardiac output, rate of rise of left ventricular pressure (dP/dt) at 40 mmHg developed pressure and calculated systemic vascular resistance were determined. Repeated gastric distension caused similar hemodynamic responses without tachyphylaxis. beta-Blockade significantly reduced the increase in dP/dt from 893 +/- 362 to 150 +/- 63 mmHg/s. alpha-Blockade significantly altered the changes in mean arterial pressure from 33 +/- 5.0 to -2 +/- 4.7 mmHg and systemic vascular resistance from 0.114 +/- 0.019 to 0.004 +/- 0.031 peripheral resistance units. Bilateral adrenalectomy significantly diminished the contractile response from 525 +/- 107 to 50 +/- 85 mmHg/s but did not significantly alter the pressor and vasoconstrictor responses. We conclude that, during passive gastric distension in cats, the increase in myocardial contractility is mediated by beta-adrenergic-receptor stimulation, whereas the arterial vasoconstrictor and pressor responses are mediated by alpha-adrenergic receptor stimulation. Additionally, during gastric distension a substantial portion of the contractile response is dependent on the integrity of the adrenal glands.     

Effect of dihomo-gamma-linolenic acid on the canine pulmonary vascular bed

The effect of dihomo-gamma-linolenic acid (DGLA), the precursor of the monoenoic prostaglandins (PG), F1alpha and E1, on the pulmonary vascular bed of the intact dog was studied under conditions of controlled pulmonary blood flow. DGLA increased pulmonary vascular resistance in a dose-related manner by constricting intrapulmonary veins and upstream segments, presumably pulmonary arteries. Intrapulmonary injection of DGLA also increased transpulmonary injection of DGLA also increased transpulmonary airway pressure, presumably by increasing airway resistance and decreasing lung compliance or both. The vasoconstrictor response, however, was independent of changes in transpulmonary pressure since similar pressor responses were obtained in ventilated and nonventilated lungs. Further, the response was not dependent on factors or elements in whole blood, since the increase in pulmonary vascular resistance occurred during perfusion with saline or dextran and was enhanced in these media. Conversion of DGLA to PGs by a lung cyclo-oxygenase appears to mediate the response, since it was blocked by indomethacin and dose not occur with injection of nonprecursor long-chain fatty acids. These data suggest that the response to DGLA is due to formation of vasoactive products in the monoenoic PG pathway.     

Relation between capillary pressure and vascular tone over the range from maximum dilatation to maximum constriction in cat skeletal muscle

An attempt was made to assess, from a large sample (n = 567), the normal level of hydrostatic capillary pressure (Pc) in resting skeletal muscle and the extent of Pc regulation as effected by strictly graded activation of metabolic and adrenergic control mechanisms over the entire physiological range of vascular tone. With the use of a new whole-organ technique, Pc towards the venous end of the capillary was continuously recorded at constant arterial pressure (100 mmHg) and under simultaneous observations of total regional vascular resistance (RT), precapillary resistance (Ra) and post-capillary resistance (RV). In the control state with a Starling fluid equilibrium, a venous pressure of 7 mmHg and normal vascular tone (RT = 19.1 +/- 0.3 PRU), Pc averaged 16.7 +/- 0.3 mmHg. Graded metabolic dilatation (muscle exercise), decreasing RT to a minimum value of 1.7 PRU, caused progressive increase in Pc up to 32 mmHg and consequent fluid filtration. Conversely, graded adrenergic constriction, increasing RT to a maximum of 100 PRU, caused a progressive decrease in Pc down to 10 mmHg and consequent fluid absorption. The relation between Pc and RT was highly non-linear, Pc increasing more steeply the more RT approached low values, and was described by the power function: Pc = 36.43 x RT-0.27 (r = -0.79, P less than 0.001). The resistance ratio, Rv/Ra (the main determinant of Pc), and vascular tone (RT) showed a similar non-linear relation. Regulatory change of Rv/Ra was mainly accomplished by active change of Ra, but a pronounced Rv decrease (venodilatation) occurred in the lowest RT range, exerting a protective function against excessive increase in Pc and detrimental plasma fluid loss.