Pulmonary vascular response to endothelin in rats

This study investigated the pulmonary vascular response to endothelin (ET) in rats. In conscious rats, an incremental intravenous bolus of ET-1 (100-1,000 pM) caused, after an initial drop in systemic arterial pressure (Psa), a secondary dose-dependent increase of Psa concomitant with a decrease of cardiac output (CO) and heart rate (HR). Pulmonary arterial pressure (Ppa) remained unchanged, and pulmonary vascular resistance (PVR) increased significantly only after 1,000 pM (+ 40.0 +/- 10.4 at 15 min). Meclofenamate (6 mg/kg iv) did not alter hemodynamic response to ET (300 pM). After autonomic blockade with hexamethonium (6 mg/kg iv) plus atropine (0.75 mg/kg iv), bradycardia response to ET (300 pM) was blocked, but CO decreased, systemic vascular resistance increased, and PVR remained unchanged as in controls. In anesthetized ventilated rats, bolus injections of ET (10-1,000 pM) induced a transient dose-related decrease in compliance (-10.9 +/- 1.8% after 1,000 pM) but no change of conductance. In isolated lungs, Ppa increased at doses greater than 100 pM, and edema developed in response to 1,000 pM ET. The rise of Ppa in response to 300 pM was not altered by meclofenamate (3.2 x 10(-6) M) but was potentiated by inhibitors of endothelium-derived relaxing factor(s) (EDRF), methylene blue (10(-4) M), pyrogallol (3 x 10(-5) M), and NG-monomethyl-L-arginine (6 x 10(-4) M) (3.9 +/- 0.3, 4.6 +/- 0.5, and 5.9 +/- 0.3 mmHg, respectively, compared with 1.5 +/- 0.5 mmHg in control lungs). These results suggest that circulating ET is a more potent constrictor of the systemic circulation than of the pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

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Measurement of airway wall blood flow in sheep by laser-Doppler flowmetry: interpretation and problems

Journal of Applied Physiology ◽

10.1152/jappl.1991.70.2.641 ◽

1991 ◽

Vol 70 (2) ◽

pp. 641-649 ◽

Cited By ~ 8

Author(s):

D. J. Godden ◽

E. M. Wagner ◽

P. D. Pare ◽

W. Mitzner ◽

E. M. Baile

Keyword(s):

Arterial Pressure ◽

Vascular Resistance ◽

Systemic Circulation ◽

Systemic Arterial Pressure ◽

Doppler Flowmetry ◽

Autonomic Blockade ◽

Initial Drop ◽

Pulmonary Arterial ◽

Isolated Lungs ◽

Dose Dependent Increase

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Chronic EDRF inhibition and hypoxia: effects on pulmonary circulation and systemic blood pressure

Journal of Applied Physiology ◽

10.1152/jappl.1993.75.4.1748 ◽

1993 ◽

Vol 75 (4) ◽

pp. 1748-1757 ◽

Cited By ~ 77

Author(s):

V. Hampl ◽

S. L. Archer ◽

D. P. Nelson ◽

E. K. Weir

Keyword(s):

Pulmonary Hypertension ◽

Arterial Pressure ◽

Chronic Hypoxia ◽

Acute Hypoxia ◽

Systemic Blood Pressure ◽

Systemic Circulation ◽

Systemic Arterial Pressure ◽

Hypoxic Pulmonary Hypertension ◽

Basal Tone ◽

Isolated Lungs

It has been suggested that chronic hypoxic pulmonary hypertension results from chronic hypoxic inhibition of endothelium-derived relaxing factor (EDRF) synthesis. We tested this hypothesis by studying whether chronic EDRF inhibition by N omega-nitro-L-arginine methyl ester (L-NAME) would induce pulmonary hypertension similar to that found in chronic hypoxia. L-NAME (1.85 mM) was given for 3 wk in drinking water to rats living in normoxia or hypoxia. Unlike chronic hypoxia, chronic L-NAME treatment did not increase pulmonary arterial pressure. Cardiac output was reduced and mean systemic arterial pressure was increased by chronic L-NAME treatment. The vascular pressure-flow relationship in isolated lungs was shifted toward higher pressures by chronic hypoxia and, to a lesser degree, by L-NAME intake. In isolated lungs, vasoconstriction in response to angiotensin II and acute hypoxia and vasodilation in response to sodium nitroprusside were increased by chronic L-NAME treatment in normoxia and chronic hypoxia. Chronic hypoxia, but not L-NAME, induced hypertensive pulmonary vascular remodeling. Chronic supplementation with the EDRF precursor L-arginine did not have any significant effect on chronic hypoxic pulmonary hypertension. We conclude that the chronic EDRF deficiency state, induced by L-NAME, does not mimic chronic hypoxic pulmonary hypertension in our model. In addition, EDRF proved to be less important for basal tone regulation in the pulmonary than in the systemic circulation.

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Inhaled nitric oxide partially reverses hypoxic pulmonary vasoconstriction in the dog

Journal of Applied Physiology ◽

10.1152/jappl.1994.76.3.1350 ◽

1994 ◽

Vol 76 (3) ◽

pp. 1350-1355 ◽

Cited By ~ 18

Author(s):

J. A. Romand ◽

M. R. Pinsky ◽

L. Firestone ◽

H. A. Zar ◽

J. R. Lancaster

Keyword(s):

Nitric Oxide ◽

Arterial Pressure ◽

Pulmonary Vascular Resistance ◽

Vascular Resistance ◽

Hypoxic Pulmonary Vasoconstriction ◽

Canine Model ◽

Systemic Arterial Pressure ◽

Vasomotor Tone ◽

Pulmonary Vasoconstriction ◽

Pulmonary Arterial

Nitric oxide (NO) inhaled during a hypoxia-induced increase in pulmonary vasomotor tone decreases pulmonary arterial pressure (Ppa). We conducted this study to better characterize the hemodynamic effects induced by NO inhalation during hypoxic pulmonary vasoconstriction in 11 anesthetized ventilated dogs. Arterial and venous systemic and pulmonary pressures and aortic flow probe-derived cardiac output were recorded, and nitrosylhemoglobin (NO-Hb) and methemoglobin (MetHb) were measured. The effects of 5 min of NO inhalation at 0, 17, 28, 47, and 0 ppm during hyperoxia (inspiratory fraction of O2 = 0.5) and hypoxia (inspiratory fraction of O2 = 0.16) were observed. NO inhalation has no measurable effects during hyperoxia. Hypoxia induced an increase in Ppa that reached plateau levels after 5 min. Exposure to 28 and 47 ppm NO induced an immediate (< 30 s) decrease in Ppa and calculated pulmonary vascular resistance (P < 0.05 each) but did not return either to baseline hyperoxic values. Increasing the concentration of NO to 74 and 145 ppm in two dogs during hypoxia did not induce any further decreases in Ppa. Reversing hypoxia while NO remained at 47 ppm further decreased Ppa and pulmonary vascular resistance to baseline values. NO inhalation did not induce decreases in systemic arterial pressure. MetHb remained low, and NO-Hb was unmeasurable. We concluded that NO inhalation only partially reversed hypoxia-induced increases in pulmonary vasomotor tone in this canine model. These effects are immediate and selective to the pulmonary circulation.

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Rho kinase and Ca2+ entry mediate increased pulmonary and systemic vascular resistance in l-NAME-treated rats

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00189.2007 ◽

2007 ◽

Vol 293 (5) ◽

pp. L1306-L1313 ◽

Cited By ~ 24

Author(s):

Jasdeep S. Dhaliwal ◽

David B. Casey ◽

Anthony J. Greco ◽

Adeleke M. Badejo ◽

Thomas B. Gallen ◽

...

Keyword(s):

Cardiac Output ◽

Arterial Pressure ◽

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Pulmonary Arterial Pressure ◽

Rho Kinase ◽

Systemic Arterial Pressure ◽

Intravenous Injections ◽

Pulmonary Arterial ◽

Dose Dependent

The small GTP-binding protein and its downstream effector Rho kinase play an important role in the regulation of vasoconstrictor tone. Rho kinase activation maintains increased pulmonary vascular tone and mediates the vasoconstrictor response to nitric oxide (NO) synthesis inhibition in chronically hypoxic rats and in the ovine fetal lung. However, the role of Rho kinase in mediating pulmonary vasoconstriction after NO synthesis inhibition has not been examined in the intact rat. To address this question, cardiovascular responses to the Rho kinase inhibitor fasudil were studied at baseline and after administration of an NO synthesis inhibitor. In the intact rat, intravenous injections of fasudil cause dose-dependent decreases in systemic arterial pressure, small decreases in pulmonary arterial pressure, and increases in cardiac output. l-NAME caused a significant increase in pulmonary and systemic arterial pressures and a decrease in cardiac output. The intravenous injections of fasudil after l-NAME caused dose-dependent decreases in pulmonary and systemic arterial pressure and increases in cardiac output, and the percent decreases in pulmonary arterial pressure in response to the lower doses of fasudil were greater than decreases in systemic arterial pressure. The Ca++ entry blocker isradipine also decreased pulmonary and systemic arterial pressure in l-NAME-treated rats. Infusion of sodium nitroprusside restored pulmonary arterial pressure to baseline values after administration of l-NAME. These data provide evidence in support of the hypothesis that increases in pulmonary and systemic vascular resistance following l-NAME treatment are mediated by Rho kinase and Ca++ entry through L-type channels, and that responses to l-NAME can be reversed by an NO donor.

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Atrial natriuretic factor attenuates the pulmonary pressor response to hypoxia

Journal of Applied Physiology ◽

10.1152/jappl.1988.65.5.1975 ◽

1988 ◽

Vol 65 (5) ◽

pp. 1975-1983 ◽

Cited By ~ 61

Author(s):

S. Adnot ◽

P. E. Chabrier ◽

C. Brun-Buisson ◽

I. Viossat ◽

P. Braquet

Keyword(s):

Arterial Pressure ◽

Vascular Resistance ◽

Atrial Natriuretic Factor ◽

Pressor Response ◽

Systemic Arterial Pressure ◽

Pulmonary Hemodynamics ◽

Natriuretic Factor ◽

Pulmonary Vasodilator ◽

Pulmonary Arterial ◽

Atrial Natriuretic

The influence of endogenous and exogenous atrial natriuretic factor (ANF) on pulmonary hemodynamics was investigated in anesthetized pigs during both normoxia and hypoxia. Continuous hypoxic ventilation with 11% O2 was associated with a uniform but transient increase of plasma immunoreactive (ir) ANF that peaked at 15 min. Plasma irANF was inversely related to pulmonary arterial pressure (Ppa; r = -0.66, P less than 0.01) and pulmonary vascular resistance (PVR; r = -0.56, P less than 0.05) at 30 min of hypoxia in 14 animals; no such relationship was found during normoxia. ANF infusion after 60 min of hypoxia in seven pigs reduced the 156 +/- 20% increase in PVR to 124 +/- 18% (P less than 0.01) at 0.01 microgram.kg-1.min-1 and to 101 +/- 15% (P less than 0.001) at 0.05 microgram.kg-1.min-1. Cardiac output (CO) and systemic arterial pressure (Psa) remained unchanged, whereas mean Ppa decreased from 25.5 +/- 1.5 to 20.5 +/- 15 mmHg (P less than 0.001) and plasma irANF increased two- to nine-fold. ANF infused at 0.1 microgram.kg-1.min-1 (resulting in a 50-fold plasma irANF increase) decreased Psa (-14%) and reduced CO (-10%); systemic vascular resistance (SVR) was not changed, nor was a further decrease in PVR induced. No change in PVR or SVR occurred in normoxic animals at any ANF infusion rate. These results suggest that ANF may act as an endogenous pulmonary vasodilator that could modulate the pulmonary pressor response to hypoxia.

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Adenosine and hypoxic pulmonary vasodilation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1984.247.4.h541 ◽

1984 ◽

Vol 247 (4) ◽

pp. H541-H547 ◽

Cited By ~ 2

Author(s):

J. E. Gottlieb ◽

M. D. Peake ◽

J. T. Sylvester

Keyword(s):

Arterial Pressure ◽

Time Course ◽

Pulmonary Arterial Pressure ◽

Autologous Blood ◽

Systemic Circulation ◽

Constant Flow ◽

Pulmonary Vasodilation ◽

Pulmonary Arterial ◽

Hypoxic Vasodilation ◽

Isolated Lungs

We have previously shown that after exposure to an inspired O2 tension less than 25 Torr, isolated lungs perfused with autologous blood exhibit vasoconstriction followed by dilation. Because adenosine has been implicated as a mediator of hypoxic vasodilation in the systemic circulation and because the concentration of adenosine in the lung has been shown to increase with hypoxia, we tested the hypothesis that adenosine is the mediator of hypoxic pulmonary vasodilation. We first confirmed that adenosine was a vasodilator in isolated lungs of adult male ferrets. Next we added the enzyme adenosine deaminase (ADase), which inactivates adenosine by converting it to inosine, to the perfusate before exposure to one of two levels of hypoxia [inspiratory PO2 (PIO2) 18 or 0 Torr]. In comparison with untreated lungs, the time course of pulmonary arterial pressure at constant flow in lungs treated with ADase (24 mg protein or 6,000 U) was not different; however, when the vessels were constricted at PIO2 25 Torr, ADase prevented vasodilator responses to adenosine administered into either the perfusate or the airways, indicating penetration of active ADase into the interstitium. Unless adenosine released endogenously into the interstitium during hypoxia was somehow protected from the ADase which reached the interstitium, these results indicate that hypoxic pulmonary vasodilation was not mediated by adenosine.

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Adrenoceptor function in the bovine pulmonary circulation

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y86-114 ◽

1986 ◽

Vol 64 (6) ◽

pp. 689-693 ◽

Cited By ~ 7

Author(s):

Kevin J. Greenlees ◽

Robert Gamble ◽

Peter Eyre

Keyword(s):

Arterial Pressure ◽

Vascular Resistance ◽

Pulmonary Arteries ◽

Systemic Arterial Pressure ◽

Venous Circulation ◽

Arterial Ph ◽

Pulmonary Arterial ◽

Dose Dependent Decrease ◽

Dose Dependent ◽

Arteries And Veins

The bovine pulmonary vascular response to α- and β-agonists was studied using an awake intact calf model. Pulmonary arterial pressure, pulmonary arterial wedge pressure, left atrial pressure, systemic arterial pressure, and cardiac output were measured in response to 3 min infusions of isoproterenol (β-agonist; 0.12, 0.24, 0.48, 0.9, and 1.8 μg∙kg−1∙min−1) and phenylephrine (α-agonist, 0.15, 0.30, 0.60, 1.15, and 2.30 μg∙kg−1∙min−1). Phenylephrine caused an increase in vascular resistance in the pulmonary arterial and venous compartments. The slope of the resistance in response to phenylephrine was greater in the pulmonary arterial than pulmonary venous circulation. Isoproterenol resulted in a dose-dependent decrease in vascular resistance in the pulmonary arteries and veins. The vascular resistance was decreased to the same level in the pulmonary arteries and veins although the arteries showed a greater percent change. In addition, isoproterenol infusion resulted in a transient decrease in arterial pH and increase in values for packed cell volume and haemoglobin.

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Cardiorespiratory Disturbances Associated with Infective Fever in Man: Studies of Ethiopian Louse-Borne Relapsing Fever

Clinical Science ◽

10.1042/cs0390123 ◽

1970 ◽

Vol 39 (1) ◽

pp. 123-145 ◽

Cited By ~ 25

Author(s):

D. A. Warrell ◽

Helen M. Pope ◽

E. H. O. Parry ◽

P. L. Perine ◽

A.D.M. Bryceson

Keyword(s):

Cardiac Output ◽

Body Temperature ◽

Arterial Pressure ◽

Metabolic Rate ◽

Vascular Resistance ◽

Pulmonary Arterial Pressure ◽

Pulmonary Ventilation ◽

Systemic Arterial Pressure ◽

Relapsing Fever ◽

Pulmonary Arterial

1. Nineteen patients with louse-borne relapsing fever were studied in Addis Abeba (altitude 2285 m). 2. Following treatment with tetracycline a febrile Jarisch—Herxheimer-like reaction developed which showed the phases described in artificially-induced endotoxin fever. 3. During the chill phase body temperature, metabolic rate and pulmonary ventilation increased. Despite alveolar hyperventilation pulmonary venous admixture was high. Cardiac output, heart rate and systemic arterial pressure increased but pulmonary arterial pressure decreased. 4. During the flush phase systemic arterial pressure fell and remained low for many hours due to reduced vascular resistance, but pulmonary arterial pressure and inflow resistance increased. Small increases in glucose, lactate, and pyruvate concentrations were prevented by inhaling oxygen. 5. Stimulation of metabolic rate, ventilation and cardiac output during the reaction was not due simply to increased body temperature, hypoxia, or acidosis but was probably attributable to spirochaetal endotoxin. 6. Limitation of pulmonary oxygen diffusion may have been responsible for the impaired pulmonary oxygen uptake in these patients. 7. During the prolonged flush phase a greatly increased cardiac output is necessary to maintain systemic arterial pressure because of the very low vascular resistance. Prevention of extracellular fluid volume depletion, early detection and prompt treatment of cardiac failure and oxygen therapy may reduce fatalities during this critical period but hydrocortisone in large doses failed to reduce the severity of the reaction.

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Hypoxia-induced alterations of norepinephrine vascular reactivity in isolated perfused cat lung

Journal of Applied Physiology ◽

10.1152/jappl.1987.63.3.982 ◽

1987 ◽

Vol 63 (3) ◽

pp. 982-987 ◽

Cited By ~ 10

Author(s):

M. Cutaia ◽

P. Friedrich

Keyword(s):

Arterial Pressure ◽

Vascular Resistance ◽

Significant Relationship ◽

Vascular Reactivity ◽

Pulmonary Arterial Pressure ◽

Pressor Response ◽

Acute Hypoxia ◽

Beta Blockade ◽

Vascular Response ◽

Pulmonary Arterial

Past work in the isolated perfused cat lung has shown that acute hypoxia (H) changes the response to norepinephrine (NE) from vasoconstriction to vasodilation but has no effect on the response to serotonin (S). These results could be related to the increase in pulmonary arterial pressure or vascular resistance during the hypoxic pressor response or a direct effect of H. We addressed this question, in the same preparation, by comparing responses to NE under four conditions in each experimental animal (n = 12): 1) NE infused during normoxia; 2) NE infused after vascular resistance (Rpv) was increased with serotonin; 3) NE infused after Rpv was increased by H; 4) NE infused after lobar pressure was raised by an increase in flow (P/F). PO2 values during H were varied (27–56 Torr). S and H produced a 137 +/- 35 and 43 +/- 8% delta Rpv increase in lobar vascular resistance, respectively. P/F increased lobar pressure 91 +/- 10%. Only NE infusion during H demonstrated significant differences in lobar pressure and Rpv compared with control normoxic periods. There was no correlation between responses to NE during S, H, and P/F and degree to which each stimulus increased Rpv or lobar pressure (r = 0.003, 0.28, 0.24). A significant relationship between response to NE during H vs. PO2 during H was observed (r = 0.78; P less than 0.001). In a subset of animals, we repeated the infusion of NE during H and P/F post-beta-blockade. The decrease in vascular response to NE during H and the correlation of PO2 with NE response were abolished (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

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