PEEP inhibits hypoxic pulmonary vasoconstriction in dogs

1991 ◽  
Vol 70 (4) ◽  
pp. 1867-1873 ◽  
Author(s):  
P. Lejeune ◽  
J. L. Vachiery ◽  
J. M. De Smet ◽  
M. Leeman ◽  
S. Brimioulle ◽  
...  
Keyword(s):  
Inferior Vena ◽  
Intact Animal ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Balloon Catheter ◽  
Vena Cava ◽  
Pulmonary Hemodynamics ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Vasoconstriction ◽  
Anesthetized Dogs ◽  
Pulmonary Arterial

The effects of an increase in alveolar pressure on hypoxic pulmonary vasoconstriction (HPV) have been reported variably. We therefore studied the effects of positive end-expiratory pressure (PEEP) on pulmonary hemodynamics in 13 pentobarbital-anesthetized dogs ventilated alternately in hyperoxia [inspired O2 fraction (FIO2) 0.4] and in hypoxia (FIO2 0.1). In this intact animal model, HPV was defined as the gradient between hypoxic and hyperoxic transmural (tm) mean pulmonary arterial pressure [Ppa(tm)] at any level of cardiac index (Q). Ppa(tm)/Q plots were constructed with mean transmural left atrial pressure [Pla(tm)] kept constant at approximately 6 mmHg (n = 5 dogs), and Ppa(tm)/PEEP plots were constructed with Q kept constant approximately 2.8 l.min-1.m-2 and Pla(tm) kept constant approximately 8 mmHg (n = 8 dogs). Q was manipulated using a femoral arteriovenous bypass and a balloon catheter in the inferior vena cava. Pla(tm) was held constant by a balloon catheter placed by left thoracotomy in the left atrium. Increasing PEEP, from 0 to 12 Torr by 2-Torr increments, at constant Q and Pla(tm), increased Ppa(tm) from 14 +/- 1 (SE) to 19 +/- 1 mmHg in hyperoxia but did not affect Ppa(tm) (from 22 +/- 2 to 23 +/- 1 mmHg) in hypoxia. Both hypoxia and PEEP, at constant Pla(tm), increased Ppa(tm) over the whole range of Q studied, from 1 to 5 l/min, but more at the highest than at the lowest Q and without change in extrapolated pressure intercepts. Adding PEEP to hypoxia did not affect Ppa(tm) at all levels of Q.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of PEEP on pulmonary hemodynamics in intact dogs with oleic acid pulmonary edema

1990 ◽  
Vol 69 (6) ◽  
pp. 2190-2196 ◽  
Author(s):  
M. Leeman ◽  
P. Lejeune ◽  
J. Closset ◽  
J. L. Vachiery ◽  
C. Melot ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Lung Injury ◽  
Balloon Catheter ◽  
Vena Cava ◽  
Linear Increase ◽  
Pulmonary Hemodynamics ◽  
Mean Pulmonary Arterial Pressure ◽  
Anesthetized Dogs ◽  
Pulmonary Arterial ◽  
The Right

The effects of positive end-expiratory pressure (PEEP) on the pulmonary circulation were studied in 14 intact anesthetized dogs with oleic acid (OA) lung injury. Transmural (tm) mean pulmonary arterial pressure (Ppa)/cardiac index (Q) plots with transmural left atrial pressure (Pla) kept constant were constructed in seven dogs, and Ppa(tm)/PEEP plots with Q and Pla(tm) kept constant were constructed in seven other dogs. Q was manipulated by using a femoral arteriovenous bypass and a balloon catheter inserted in the inferior vena cava. Pla was manipulated using a balloon catheter placed by thoracotomy in the left atrium. Ppa(tm)/Q plots were essentially linear. Before OA, the linearly extrapolated pressure intercept of the Ppa(tm)/Q relationship approximated Pla(tm). OA (0.09 ml/kg into the right atrium) produced a parallel shift of the Ppa(tm)/Q relationship to higher pressures; i.e., the extrapolated pressure intercept increased while the slope was not modified. After OA, 4 Torr PEEP (5.4 cmH2O) had no effect on the Ppa(tm)/Q relationship and 10 Torr PEEP (13.6 cmH2O) produced a slight, not significant, upward shift of this relationship. Changing PEEP from 0 to 12 Torr (16.3 cmH2O) at constant Q before OA led to an almost linear increase of Ppa(tm) from 14 +/- 1 to 19 +/- 1 mmHg. After OA, Ppa(tm) increased at 0 Torr PEEP but changing PEEP from 0 to 12 Torr did not significantly affect Ppa(tm), which increased from 19 +/- 1 to 20 +/- 1 mmHg. These data suggest that moderate levels of PEEP minimally aggravate the pulmonary hypertension secondary to OA lung injury.

Relationship of leukotriene C4 and D4 to hypoxic pulmonary vasoconstriction in dogs

1988 ◽  
Vol 64 (6) ◽  
pp. 2538-2543 ◽  
Author(s):  
A. J. Lonigro ◽  
R. S. Sprague ◽  
A. H. Stephenson ◽  
T. E. Dahms
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Lavage Fluid ◽  
Pulmonary Hemodynamics ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Vasoconstriction ◽  
Time Period ◽  
Pulmonary Arterial ◽  
Synthase Inhibitor ◽  
Leukotriene A4 ◽  
Relationship Of

Leukotrienes C4 and D4 have been implicated as possible mediators of hypoxic pulmonary vasoconstriction. To test this hypothesis, the relationship between pulmonary leukotriene (LT) synthesis in response to hypoxia and alterations in pulmonary hemodynamics was evaluated in pentobarbital sodium-anesthetized, neuromuscular-blocked, male, mongrel dogs. A reduction in the fraction of inspired O2 (FIO2) in vehicle-treated animals (n = 12) from 0.21 to 0.10 was associated with increases in LTC4 and LTD4 in bronchoalveolar lavage fluid (BALF). After 30 min of continuous hypoxia, LTC4 and LTD4 increased from control values of 59.4 +/- 10.4 and 91.7 +/- 18.1 ng/lavage to 142.7 +/- 31.8 (P less than 0.05) and 156.3 +/- 25.3 (P less than 0.01) ng/lavage, respectively. Concomitantly, mean pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (PVR) were increased over control by 67 +/- 7 (P less than 0.001) and 62 +/- 7% (P less than 0.001), respectively. In contrast, in animals treated with diethylcarbamazine (n = 5), a leukotriene A4 synthase inhibitor, identical reductions in FIO2 were not associated with increases in LTC4 and LTD4 in BALF, although at the same time period, Ppa and PVR were increased over control by 60 +/- 13 (P less than 0.05) and 112 +/- 31% (P less than 0.05), respectively. These results, therefore, do not support the contention that leukotrienes mediate hypoxic pulmonary vasoconstriction in dogs.

Inhibition of hypoxic pulmonary vasoconstriction by increased left atrial pressure in dogs

1990 ◽  
Vol 259 (1) ◽  
pp. H93-H100 ◽  
Author(s):  
P. Lejeune ◽  
J. M. De Smet ◽  
P. de Francquen ◽  
M. Leeman ◽  
S. Brimioulle ◽  
...  
Keyword(s):  
Left Atrial ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Atrial Pressure ◽  
Left Atrial Pressure ◽  
Experimental Conditions ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Vasoconstriction ◽  
Anesthetized Dogs ◽  
Pulmonary Arterial ◽  
The Mean

To further explore the mechanism of hypoxic pulmonary vasoconstriction, we studied the mean pulmonary arterial pressure (Ppa)/left atrial pressure (Pla) relationship at fixed cardiac index (Q) and the Ppa/Q relationship at several levels of fixed Pla in pentobarbital sodium-anesthetized dogs ventilated alternately in hyperoxia [fraction of inspired O2 (FIO2) 0.4 or 1.0] and in hypoxia (FIO2 0.1). In all experimental conditions, Ppa/Q plots were linear with extrapolated pressure intercepts (Pi) not significantly different from Pla. Hypoxia increased the slope of Ppa/Q plots and did not affect Pi. In hyperoxia, increasing Pla (3 to 26 mmHg) induced approximately equal increases in Ppa at fixed Q and shifted Ppa/Q plots toward higher pressures in a parallel manner. In hypoxia, increasing Pla (4 to 25 mmHg) did not affect Ppa at fixed Q until Pla exceeded 16 mmHg and shifted Ppa/Q plots toward higher pressures with a decrease in slope. Consequently, the hypoxia-induced increases in Ppa at constant Q and constant Pla were attenuated at higher Pla. Thus, in anesthetized dogs, hypoxia increases the slope of Ppa/Q plots without affecting Pi at fixed Pla, and an increase in Pla inhibits hypoxic pulmonary vasoconstriction. These results can be explained without invoking a hypoxia-induced Starling resistor mechanism in the pulmonary circulation.

Prostaglandin D2 inhibits hypoxic pulmonary vasoconstriction in neonatal lambs

1983 ◽  
Vol 54 (6) ◽  
pp. 1585-1589 ◽  
Author(s):  
J. B. Philips ◽  
R. K. Lyrene ◽  
M. McDevitt ◽  
W. Perlis ◽  
C. Satterwhite ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Inferior Vena ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Vena Cava ◽  
Systemic Arterial Pressure ◽  
Prostaglandin D2 ◽  
Pulmonary Vasoconstriction ◽  
Neonatal Lambs

Intrapulmonary injections of prostaglandin D2 (PGD2) reduce pulmonary arterial pressure and resistance in fetal and hypoxic neonatal lambs without affecting systemic arterial pressure. This apparently specific pulmonary effect of PGD2 could be explained by inactivation of the agent during passage through the pulmonary capillary bed. We therefore studied the effects of both pulmonary and systemic infusions of PGD2 on the acute vascular response to a 1-min episode of hypoxia in newborn lambs. Since PGD2 has been reported to be a pulmonary vasoconstrictor in normoxic lambs, we also evaluated its effects during normoxemia. Pulmonary vascular pressures were not affected by either 1- or 10-micrograms . kg-1 . min-1 infusions into the left atrium or inferior vena cava during normoxia. Infusion of 1 microgram . kg-1 . min-1 PGD2 into the inferior vena cava decreased pulmonary vascular resistance and increased systemic arterial pressure. These two parameters were unchanged with the other three infusion regimens. Mean pulmonary vascular resistance rose 83% with hypoxia and no PGD2. PGD2 prevented any change in pulmonary vascular resistance with hypoxia, while systemic arterial pressure increased (1-microgram . kg-1 . min-1 doses) or was unchanged. Thus PGD2 specifically prevents hypoxic pulmonary vasoconstriction while maintaining systemic pressures, regardless of infusion site. PGD2 may be indicated in treatment of persistent pulmonary hypertension of the newborn and other pulmonary hypertensive disorders.

Pulmonary vascular impedance vs. resistance in hypoxic and hyperoxic dogs: effects of propofol and isoflurane

1993 ◽  
Vol 74 (5) ◽  
pp. 2188-2193 ◽  
Author(s):  
P. Ewalenko ◽  
C. Stefanidis ◽  
A. Holoye ◽  
S. Brimioulle ◽  
R. Naeije
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Vasculature ◽  
Hemodynamic Changes ◽  
Vascular Effects ◽  
Intravenous Anesthesia ◽  
Mean Pulmonary Arterial Pressure ◽  
Vascular Impedance ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial ◽  
The Time Domain

The pulmonary vascular effects of inhaled anesthetics have been reported variably. We compared the effects of intravenous anesthesia (propofol) and inhalational anesthesia (isoflurane) on multipoint mean [pulmonary arterial pressure (Ppa)-pulmonary arterial occluded pressure (PpaO)]/cardiac output (Q) plots and on pulmonary vascular impedance (PVZ) spectra in eight dogs alternatively ventilated in hyperoxia [inspired O2 fraction (FIO2) 0.4] and in hypoxia (FIO2 0.1). Q was altered by a manipulation of venous return. During propofol, hypoxia increased (Ppa-PpaO) by an average of 2–3 mmHg over the entire range of Q studied, from 1 to 2.5 l.min-1 x m-2. This hypoxic pulmonary vasoconstriction (HPV) was associated with insignificant changes in PVZ. Decreasing Q in hypoxia and hyperoxia did not affect PVZ. Compared with propofol, isoflurane decreased (Ppa-PpaO) by an average of 2–5 mmHg at all levels of Q studied in both hypoxia and hyperoxia but did not affect HPV. During isoflurane anesthesia, 0 Hz PVZ was lower (P < 0.01) in hypoxia, but otherwise the PVZ spectrum was not different from that recorded during propofol anesthesia. We conclude that, in dogs, 1 degree general anesthesia with isoflurane alone decreases pulmonary vascular tone without inhibition of HPV and that 2 degrees pressure/Q plots in the time domain are more sensitive than those in the frequency domain to subtle hemodynamic changes induced by hypoxia or isoflurane at the periphery of the pulmonary vasculature.

scholarly journals Pulmonary vasodilation by acetazolamide during hypoxia: impact of methyl-group substitutions and administration route in conscious, spontaneously breathing dogs

2014 ◽  
Vol 116 (7) ◽  
pp. 715-723 ◽  
Author(s):  
Philipp A. Pickerodt ◽  
Roland C. Francis ◽  
Claudia Höhne ◽  
Friederike Neubert ◽  
Stella Telalbasic ◽  
...  
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Acute Hypoxia ◽  
Administration Routes ◽  
Pulmonary Vasodilation ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Vasoconstriction ◽  
Thiadiazole Ring ◽  
Pulmonary Arterial ◽  
Isolated Lungs ◽  
Spontaneously Breathing

Acetazolamide (ACZ) prevents hypoxic pulmonary vasoconstriction (HPV) in isolated lungs, animals, and humans, but not by carbonic anhydrase (CA) inhibition. We studied administration routes in, and certain structural aspects of, ACZ critical to HPV inhibition. Analogs of ACZ during acute hypoxia were tested in unanesthetized dogs. Dogs breathed normoxic gas for 1 h (inspired O2 fraction = 0.21), followed by 10% O2 for 2 h (hypoxia) in these protocols: 1) controls; 2) ACZ intravenously (2 mg·kg−1·h−1); 3) ACZ orally (5 mg/kg, 12 and 1 h before the experiment); 4) inhaled ACZ (750 mg); 5) methazolamide (MTZ) intravenously (3 mg·kg−1·h−1); and 6) N-methyl-acetazolamide (NMA) intravenously (10 mg·kg−1·h−1). In controls, mean pulmonary arterial pressure (MPAP) increased 7 mmHg, and pulmonary vascular resistance (PVR) 224 dyn·s·cm−5 with hypoxia ( P < 0.05). With intravenous and inhaled ACZ, MPAP and PVR did not change during hypoxia. With oral ACZ, HPV was only slightly suppressed; MPAP increased 5 mmHg and PVR by 178 dyn·s·cm−5 during hypoxia. With MTZ and NMA, the MPAP rise (4 ± 2 mmHg) was reduced, and PVR did not increase during hypoxia compared with normoxia (MTZ intravenous: 81 ± 77 and 68 ± 82 dyn·s·cm−5 with NMA intravenous). Inhaled ACZ prevents HPV, but not without causing systemic CA inhibition. NMA, a compound lacking CA inhibiting effects by methylation at the sulfonamide moiety, and MTZ, a CA-inhibiting analog methylated at the thiadiazole ring, are only slightly less effective than ACZ in reducing HPV.

Increased left atrial pressure inhibits hypoxic pulmonary vasoconstriction

1994 ◽  
Vol 76 (4) ◽  
pp. 1502-1506 ◽  
Author(s):  
D. De Canniere ◽  
C. Stefanidis ◽  
R. Hallemans ◽  
M. Delcroix ◽  
P. Lejeune ◽  
...  
Keyword(s):  
Left Atrial ◽  
Pressor Response ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Vena Cava ◽  
Atrial Pressure ◽  
Left Atrial Pressure ◽  
Experimental Conditions ◽  
Balloon Catheters ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Vasoconstriction

An increase in left atrial pressure (Pla) has been reported to either inhibit or not affect hypoxic pulmonary vasoconstriction in intact dogs. We investigated mean pulmonary arterial pressure (Ppa)-flow (Q) relationships at low and high fixed Pla and Ppa-Pla relationships at fixed Q in piglets, which are known to present with a stronger hypoxic pulmonary pressor response than dogs. Seven piglets were anesthetized; equipped with balloon catheters in inferior vena cava and left atrium to control Q and Pla, respectively; and ventilated alternatively in hyperoxia [fractional concn of O2 in inspired air (FIO2) 0.4] and hypoxia (FIO2 0.12). In all experimental conditions, Ppa-Q plots were best described by a linear approximation with extrapolated pressure intercepts (Pi) not different from Pla. Hypoxia increased slope but not Pi of Ppa-Q plots. An increase in Pla from 8 to 17 mmHg induced a parallel shift of Ppa-Q plots to higher Ppa in hyperoxia but did not affect Ppa-Q plots in hypoxia. In hyperoxia, an increase in Pla at constant Q induced an approximately equal increase in Ppa, whereas in hypoxia there was no effect. The hypoxia-induced increase in Ppa was blunted by increased Pla at all levels of Q studied. We conclude that in anesthetized piglets at fixed Pla hypoxia increases the slope of Ppa-Q plots without affecting Pi and an increase in Pla inhibits hypoxic pulmonary vasoconstriction. The results suggest that no closing pressure higher than normal Pla contributes to hyperoxic or hypoxic Ppa in the intact porcine pulmonary circulation.

Hypoxic pulmonary vasoconstriction and gas exchange in acute canine pulmonary embolism

1996 ◽  
Vol 80 (4) ◽  
pp. 1240-1248 ◽  
Author(s):  
M. Delcroix ◽  
C. Melot ◽  
F. Vermeulen ◽  
R. Naeije
Keyword(s):  
Pulmonary Embolism ◽  
Gas Exchange ◽  
Sulfur Hexafluoride ◽  
Blood Clot ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Autologous Blood ◽  
Response Curves ◽  
Pulmonary Hemodynamics ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial

Hypoxic pulmonary vasoconstriction (HPV) is inhibited in several models of acute lung injury. Whether HPV is preserved in pulmonary embolism is unknown. We investigated the effects of a reduction in the fraction of inspired O2 (FIO2) on pulmonary hemodynamics and gas exchange in anesthetized dogs before and after autologous blood clot pulmonary embolism. In a first group of 14 dogs, stimulus-response curves for HPV were constructed as pulmonary arterial pressure (Ppa) vs. FIO2 varied between 1.0 and 0.06 at a cardiac output (Q) kept constant at 3.5 l.min-1.m-2. Gas exchange was evaluated by using the multiple inert-gas elimination technique at FIO2 of 1.0, 0.4, and 0.1. Embolism decreased the relative magnitude of HPV, expressed as the gradient between Ppa and pulmonary arterial occluded pressure in hypoxia divided by (Ppa-pulmonary arterial occluded pressure) at FIO2 of 1.0, from 1.8 to 1.2 (P < 0.05). Retention minus excretion gradients for sulfur hexafluoride and ethane were increased by decreased FIO2 (P < 0.005 and P < 0.05, respectively) before but not after embolism. Hypoxia-induced deterioration in gas exchange before embolism was related to the amount of baseline very low ventilation-perfusion (VA/Q) ratios. Similar results were obtained in a second group of seven dogs with Q decreased to maintain Ppa at the same average value as before embolism. However, gas exchange was not affected by inspiratory hypoxia before as well as after embolism in this group, which presented with a lesser amount of baseline very low VA/Q. In both groups of dogs, increase in the FIO2 from 0.4 to 1.0 did not affect gas exchange. We conclude that 1) pulmonary embolism is associated with a partial inhibition of HPV, 2) HPV does not contribute to preserve gas exchange in pulmonary embolism, and 3) a strong HPV may deteriorate gas exchange in severe hypoxia in the presence of minor very low VA/Q inequality.

Inhalation of the ETAreceptor antagonist LU-135252 selectively attenuates hypoxic pulmonary vasoconstriction

2008 ◽  
Vol 294 (2) ◽  
pp. R601-R605 ◽  
Author(s):  
Bodil Petersen ◽  
Maria Deja ◽  
Roland Bartholdy ◽  
Bernd Donaubauer ◽  
Sven Laudi ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Receptor Antagonist ◽  
Experimental Model ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Vasculature ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial ◽  
To Receive

Endogenous endothelin (ET)-1 modulates hypoxic pulmonary vasoconstriction (HPV). Accordingly, intravenously applied ETAreceptor antagonists reduce HPV, but this is accompanied by systemic vasodilation. We hypothesized that inhalation of an ETAreceptor antagonist might act selectively on the pulmonary vasculature and investigated the effects of aerosolized LU-135252 in an experimental model of HPV. Sixteen piglets (weight: 25 ± 1 kg) were anesthetized and mechanically ventilated at an inspiratory oxygen fraction (FiO2) of 0.3. After 1 h of hypoxia at FiO20.15, animals were randomly assigned either to receive aerosolized LU-135252 as bolus (0.3 mg/kg for 20 min; n = 8, LU group), or to receive aerosolized saline ( n = 8, controls). In all animals, hypoxia significantly increased mean pulmonary arterial pressure (32 ± 1 vs. 23 ± 1 mmHg; P < 0.01; means ± SE) and increased arterial plasma ET-1 (0.52 ± 0.04 vs. 0.37 ± 0.05 fmol/ml; P < 0.01) compared with mild hyperoxia at FiO20.3. Inhalation of LU-135252 induced a significant and sustained decrease in mean pulmonary arterial pressure compared with controls (LU group: 27 ± 1 mmHg; controls: 32 ± 1 mmHg; values at 4 h of hypoxia; P < 0.01). In parallel, mean systemic arterial pressure and cardiac output remained stable and were not significantly different from control values. Consequently, in our experimental model of HPV, the inhaled ETAreceptor antagonist LU-135252 induced selective pulmonary vasodilation without adverse systemic hemodynamic effects.

Effects of endogenous nitric oxide on pulmonary vascular tone in intact dogs

1994 ◽  
Vol 266 (6) ◽  
pp. H2343-H2347 ◽  
Author(s):  
M. Leeman ◽  
V. Z. de Beyl ◽  
M. Delcroix ◽  
R. Naeije
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Pulmonary Artery ◽  
Vascular Tone ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Balloon Catheter ◽  
Hypoxic Response ◽  
Pulmonary Vasoconstriction ◽  
Endogenous Nitric Oxide ◽  
Anesthetized Dogs

The interaction between inspiratory fraction of O2 (FIO2) and endogenous nitric oxide (NO) regulation of pulmonary vascular tone was examined in intact anesthetized dogs. Stimulus (FIO2 of 1, 0.4, 0.21, 0.12, and 0.1)-response (changes in pulmonary artery pressure minus pulmonary artery occlusion pressure) curves were constructed with cardiac output kept constant (by opening a femoral arteriovenous bypass or inflating an inferior vena cava balloon catheter), before and after administration of compounds acting at different levels of the L-arginine-NO pathway, NG-nitro-L-arginine (L-NNA, 10 mg/kg iv, n = 16), a NO synthase inhibitor, and methylene blue (8 mg/kg iv, n = 16), a guanylate cyclase inhibitor. L-NNA and methylene blue did not influence pulmonary vascular tone in hyperoxic and in normoxic conditions, but they increased it during hypoxia, thus enhancing the vasopressor response to hypoxia (from 4.5 +/- 0.9 to 10.4 +/- 1.2 mmHg and from 4.2 +/- 0.8 to 9 +/- 1.5 mmHg, respectively, both P < 0.01). Hypoxic pulmonary vasoconstriction was augmented in dogs with a baseline hypoxic response (“responders”) and restored in dogs without hypoxic response (“nonresponders”). These results suggest that endogenous NO does not influence hyperoxic and normoxic pulmonary vascular tone, but that it inhibits hypoxic pulmonary vasoconstriction in intact anesthetized dogs.

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