Endothelium-Derived Nitric Oxide Regulates Systemic and Pulmonary Vascular Resistance During Acute Hypoxia in Humans

Resuscitation with 21% O2 may not achieve target oxygenation in preterm infants and in neonates with persistent pulmonary hypertension of the newborn (PPHN). Inhaled nitric oxide (iNO) at birth can reduce pulmonary vascular resistance (PVR) and improve PaO2. We studied the effect of iNO on oxygenation and changes in PVR in preterm lambs with and without PPHN during resuscitation and stabilization at birth. Preterm lambs with and without PPHN (induced by antenatal ductal ligation) were delivered at 134 d gestation (term is 147–150 d). Lambs without PPHN were ventilated with 21% O2, titrated O2 to maintain target oxygenation or 21% O2 + iNO (20 ppm) at birth for 30 min. Preterm lambs with PPHN were ventilated with 50% O2, titrated O2 or 50% O2 + iNO. Resuscitation with 21% O2 in preterm lambs and 50%O2 in PPHN lambs did not achieve target oxygenation. Inhaled NO significantly decreased PVR in all lambs and increased PaO2 in preterm lambs ventilated with 21% O2 similar to that achieved by titrated O2 (41 ± 9% at 30 min). Inhaled NO increased PaO2 to 45 ± 13, 45 ± 20 and 76 ± 11 mmHg with 50% O2, titrated O2 up to 100% and 50% O2 + iNO, respectively, in PPHN lambs. We concluded that iNO at birth reduces PVR and FiO2 required to achieve target PaO2.

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Ultra Pure Nitric Oxide Generated Through Ascorbic Acid Reduction Of Nitrogen Dioxide Reverses Pulmonary Hypertension And Pulmonary Vascular Resistance In Hypoxemic Swine

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a5973 ◽

2011 ◽

Author(s):

Mark A. Lovich ◽

Natalie K. Bruno ◽

Abraham E. Wei ◽

Richard J. Gilbert

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Ascorbic Acid ◽

Nitrogen Dioxide ◽

Pulmonary Vascular Resistance ◽

Vascular Resistance ◽

Acid Reduction

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Inhaled Nitric Oxide Selectively Decreases Pulmonary Artery Pressure and Pulmonary Vascular Resistance Following Acute Massive Pulmonary Microembolism in Piglets

CHEST Journal ◽

10.1378/chest.110.4.1041 ◽

1996 ◽

Vol 110 (4) ◽

pp. 1041-1047 ◽

Cited By ~ 65

Author(s):

Bernd W. Böttiger ◽

Johann Motsch ◽

Joachim Dörsam ◽

Ulf Mieck ◽

André Gries ◽

...

Keyword(s):

Nitric Oxide ◽

Pulmonary Artery ◽

Pulmonary Vascular Resistance ◽

Pulmonary Artery Pressure ◽

Vascular Resistance ◽

Inhaled Nitric Oxide ◽

Artery Pressure

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Inhaled nitric oxide in patients with normal and increased pulmonary vascular resistance after cardiac surgery

British Journal of Anaesthesia ◽

10.1093/bja/72.2.185 ◽

1994 ◽

Vol 72 (2) ◽

pp. 185-189 ◽

Cited By ~ 52

Author(s):

D.J. SNOW ◽

S.Y. GRAY ◽

S. GHOSH ◽

L. FOUBERT ◽

A. ODURO ◽

...

Keyword(s):

Nitric Oxide ◽

Cardiac Surgery ◽

Pulmonary Vascular Resistance ◽

Vascular Resistance ◽

Inhaled Nitric Oxide

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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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Inhaled nitric oxide inhibits NOS activity in lambs: potential mechanism for rebound pulmonary hypertension

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.277.5.h1849 ◽

1999 ◽

Vol 277 (5) ◽

pp. H1849-H1856 ◽

Cited By ~ 23

Author(s):

Stephen M. Black ◽

R. Scott Heidersbach ◽

D. Michael McMullan ◽

Janine M. Bekker ◽

Michael J. Johengen ◽

...

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Pulmonary Vascular Resistance ◽

Vascular Resistance ◽

Inhaled Nitric Oxide ◽

Protein Levels ◽

Acute Withdrawal ◽

Inhaled No

Life-threatening increases in pulmonary vascular resistance have been noted on acute withdrawal of inhaled nitric oxide (NO), although the mechanisms remain unknown. In vitro data suggest that exogenous NO exposure inhibits endothelial NO synthase (NOS) activity. Thus the objectives of this study were to determine the effects of inhaled NO therapy and its acute withdrawal on endogenous NOS activity and gene expression in vivo in the intact lamb. Six 1-mo-old lambs were mechanically ventilated and instrumented to measure vascular pressures and left pulmonary blood flow. Inhaled NO (40 ppm) acutely decreased left pulmonary vascular resistance by 27.5 ± 4.7% ( P < 0.05). This was associated with a 207% increase in plasma cGMP concentrations ( P < 0.05). After 6 h of inhaled NO, NOS activity was reduced to 44.3 ± 5.9% of pre-NO values ( P < 0.05). After acute withdrawal of NO, pulmonary vascular resistance increased by 52.1 ± 11.6% ( P < 0.05) and cGMP concentrations decreased. Both returned to pre-NO values within 60 min. One hour after NO withdrawal, NOS activity increased by 48.4 ± 19.1% to 70% of pre-NO values ( P < 0.05). Western blot analysis revealed that endothelial NOS protein levels remained unchanged throughout the study period. These data suggest a role for decreased endogenous NOS activity in the rebound pulmonary hypertension noted after acute withdrawal of inhaled NO.

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