Pulmonary Vasoconstriction during Regional Nitric Oxide Inhalation

2001 ◽  
Vol 95 (1) ◽  
pp. 102-112 ◽  
Author(s):  
Kristina Hambraeus-Jonzon ◽  
Luni Chen ◽  
Filip Fredén ◽  
Peter Wiklund ◽  
Göran Hedenstierna
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Lung Tissue ◽  
Pulmonary Blood Flow ◽  
Inhaled Nitric Oxide ◽  
No Production ◽  
Pulmonary Vasodilation ◽  
Distant Effect ◽  
Nitric Oxide Concentration ◽  
Fraction Of Inspired Oxygen

Background Inhaled nitric oxide (INO) is thought to cause selective pulmonary vasodilation of ventilated areas. The authors previously showed that INO to a hyperoxic lung increases the perfusion to this lung by redistribution of blood flow, but only if the opposite lung is hypoxic, indicating a more complex mechanism of action for NO. The authors hypothesized that regional hypoxia increases NO production and that INO to hyperoxic lung regions (HL) can inhibit this production by distant effect. Methods Nitric oxide concentration was measured in exhaled air (NO(E)), NO synthase (NOS) activity in lung tissue, and regional pulmonary blood flow in anesthetized pigs with regional left lower lobar (LLL) hypoxia (fraction of inspired oxygen [FIO2] = 0.05), with and without INO to HL (FIO2 = 0.8), and during cross-circulation of blood from pigs with and without INO. Results Left lower lobar hypoxia increased exhaled NO from the LLL (NO(E)LLL) from a mean (SD) of 1.3 (0.6) to 2.2 (0.9) parts per billion (ppb) (P < 0.001), and Ca2+-dependent NOS activity was higher in hypoxic than in hyperoxic lung tissue (197 [86] vs. 162 [96] pmol x g(-1) x min(-1), P < 0.05). INO to HL decreased the Ca2+-dependent NOS activity in hypoxic tissue to 49 [56] pmol x g(-1) x min(-1) (P < 0.01), and NO(E)LLL to 2.0 [0.8] ppb (P < 0.05). When open-chest pigs with LLL hypoxia received blood from closed-chest pigs with INO, NO(E)LLL decreased from 2.0 (0.6) to 1.5 (0.4) ppb (P < 0.001), and the Ca2+-dependent NOS activity in hypoxic tissue decreased from 152 (55) to 98 (34) pmol x g(-1) x min(-1) (P = 0.07). Pulmonary vascular resistance increased by 32 (21)% (P < 0.05), but more so in hypoxic (P < 0.01) than in hyperoxic (P < 0.05) lung regions, resulting in a further redistribution (P < 0.05) of pulmonary blood flow away from hypoxic to hyperoxic lung regions. Conclusions Inhaled nitric oxide downregulates endogenous NO production in other, predominantly hypoxic, lung regions. This distant effect is blood-mediated and causes vasoconstriction in lung regions that do not receive INO.

scholarly journals Progressive dysfunction of nitric oxide synthase in a lamb model of chronically increased pulmonary blood flow: a role for oxidative stress

2008 ◽  
Vol 295 (5) ◽  
pp. L756-L766 ◽  
Author(s):  
Peter E. Oishi ◽  
Dean A. Wiseman ◽  
Shruti Sharma ◽  
Sanjiv Kumar ◽  
Yali Hou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Blood Flow ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Lung Tissue ◽  
Pulmonary Blood Flow ◽  
Artery Pressure ◽  
Oxide Synthase ◽  
Inhaled No

Cardiac defects associated with increased pulmonary blood flow result in pulmonary vascular dysfunction that may relate to a decrease in bioavailable nitric oxide (NO). An 8-mm graft (shunt) was placed between the aorta and pulmonary artery in 30 late gestation fetal lambs; 27 fetal lambs underwent a sham procedure. Hemodynamic responses to ACh (1 μg/kg) and inhaled NO (40 ppm) were assessed at 2, 4, and 8 wk of age. Lung tissue nitric oxide synthase (NOS) activity, endothelial NOS (eNOS), neuronal NOS (nNOS), inducible NOS (iNOS), and heat shock protein 90 (HSP90), lung tissue and plasma nitrate and nitrite (NOx), and lung tissue superoxide anion and nitrated eNOS levels were determined. In shunted lambs, ACh decreased pulmonary artery pressure at 2 wk ( P < 0.05) but not at 4 and 8 wk. Inhaled NO decreased pulmonary artery pressure at each age ( P < 0.05). In control lambs, ACh and inhaled NO decreased pulmonary artery pressure at each age ( P < 0.05). Total NOS activity did not change from 2 to 8 wk in control lambs but increased in shunted lambs (ANOVA, P < 0.05). Conversely, NOxlevels relative to NOS activity were lower in shunted lambs than controls at 4 and 8 wk ( P < 0.05). eNOS protein levels were greater in shunted lambs than controls at 4 wk of age ( P < 0.05). Superoxide levels increased from 2 to 8 wk in control and shunted lambs (ANOVA, P < 0.05) and were greater in shunted lambs than controls at all ages ( P < 0.05). Nitrated eNOS levels were greater in shunted lambs than controls at each age ( P < 0.05). We conclude that increased pulmonary blood flow results in progressive impairment of basal and agonist-induced NOS function, in part secondary to oxidative stress that decreases bioavailable NO.

Response to Inhaled Nitric Oxide in Acute Lung Injury Depends on Distribution of Pulmonary Blood Flow Prior to Its Administration

1999 ◽  
Vol 159 (2) ◽  
pp. 563-570 ◽  
Author(s):  
RENÉ GUST ◽  
TIMOTHY J. McCARTHY ◽  
JAMES KOZLOWSKI ◽  
ALAN H. STEPHENSON ◽  
DANIEL P. SCHUSTER
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Blood Flow ◽  
Inhaled Nitric Oxide

ALTERATIONS IN ENDOTHELIAL FUNCTION DURING INHALED NITRIC OXIDE (INO) IN LAMBS WITH INCREASED PULMONARY BLOOD FLOW

2002 ◽  
Vol 30 (Supplement) ◽  
pp. A1
Author(s):  
Gregory A Ross ◽  
Boaz Ovadia ◽  
Robert K Fitzgerald ◽  
Olaf Reinhartz ◽  
Jeffrey R Fineman
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Endothelial Function ◽  
Pulmonary Blood Flow ◽  
Inhaled Nitric Oxide

Inhaled nitric oxide improves oxygenation in very premature infants with low pulmonary blood flow

2007 ◽  
Vol 93 (1) ◽  
pp. 66-69 ◽  
Author(s):  
R Desandes ◽  
E Desandes ◽  
P Droullé ◽  
F Didier ◽  
D Longrois ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Premature Infants ◽  
Pulmonary Blood Flow ◽  
Inhaled Nitric Oxide ◽  
Very Premature Infants

No redistribution of lung blood flow by inhaled nitric oxide in endotoxemic piglets pretreated with an endothelin receptor antagonist

2015 ◽  
Vol 118 (6) ◽  
pp. 768-775 ◽  
Author(s):  
Sebastien Trachsel ◽  
Kristina Hambraeus-Jonzon ◽  
Maria Bergquist ◽  
Cecile Martijn ◽  
Luni Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Mrna Expression ◽  
Inhaled Nitric Oxide ◽  
Endothelin Receptor ◽  
Expression Ratio ◽  
Mechanically Ventilated ◽  
Pulmonary Vasodilation ◽  
Endothelin Receptor A ◽  
Lung Blood Flow

Inhaled nitric oxide (INO) improves ventilation-perfusion matching and alleviates pulmonary hypertension in patients with acute respiratory distress syndrome. However, outcome has not yet been shown to improve, and nonresponse is common. A better understanding of the mechanisms by which INO acts may guide in improving treatment with INO in patients with severe respiratory failure. We hypothesized that INO may act not only by vasodilation in ventilated lung regions, but also by causing vasoconstriction via endothelin (ET-1) in atelectatic, nonventilated lung regions. This was studied in 30 anesthetized, mechanically ventilated piglets. The fall in oxygenation and rise in pulmonary artery pressure during a sepsislike condition (infusion of endotoxin) were blunted by INO 40 ppm. Endotoxin infusion increased serum ET-1, and INO almost doubled the ratio between mRNA expression of endothelin receptor A (mediating vasoconstriction) and B (mediating vasodilation and clearance of ET-1) (ET-A/ET-B) in atelectatic lung regions. INO caused a shift in blood flow away from atelectatic lung regions in the endotoxemic piglets, but not during ET receptor antagonism. We conclude that INO in short-term experiments, in addition to causing selective pulmonary vasodilation in ventilated lung regions, increases the ET-A/ET-B mRNA expression ratio in lung tissue. This might augment the vasoconstriction in atelectatic lung regions, enhancing the redistribution of pulmonary blood flow to ventilated lung regions which are reached by INO. Such vasoconstriction may be an important additional factor explaining the effect of INO.

Pulmonary response of normal human subjects to inhaled vasodilator substances

1998 ◽  
Vol 95 (5) ◽  
pp. 621-627 ◽  
Author(s):  
S. J. BRETT ◽  
J. CHAMBERS ◽  
A. BUSH ◽  
M. ROSENTHAL ◽  
T. W. EVANS
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Pulmonary Blood Flow ◽  
Inhaled Nitric Oxide ◽  
Prostaglandin I2 ◽  
Vascular Bed ◽  
Normal Individuals ◽  
Chronic Pulmonary Hypertension ◽  
Pulmonary Vascular Bed

1.Inhaled vasodilators such as nitric oxide and epoprostenol (prostaglandin I2) are now widely employed as supportive therapies to improve oxygenation and reduce pulmonary vascular resistance in patients with acute and chronic pulmonary hypertension. However, few data exist concerning their effects in normal individuals. The aim of this study was to characterize the response of the pulmonary circulation in normal individuals to inhaled nitric oxide and nebulized prostaglandin I2. 2.Eight healthy volunteers were exposed to inhaled nitric oxide (0, 20 and 40 ;p.p.m.) and nebulized prostaglandin I2 (10 ;μg/ml). Changes in effective pulmonary blood flow and diffusing capacity of the lung for carbon monoxide (TLCO) were measured using respiratory mass spectrometry. Bicycle ergometry was used to increase effective pulmonary blood flow as a positive control. 3.Exercise produced significant increases in both effective pulmonary blood flow and TLCO, but neither nitric oxide nor prostaglandin I2 produced significant changes in either parameter. 4.No significant change in pulmonary haemodynamics was demonstrated in response to inhaled nitric oxide or nebulized prostaglandin I2, using doses known to be effective in patients with acute and chronic pulmonary hypertension. These data suggest that the normal pulmonary vascular bed is not amenable to vasodilatation by inhaled drugs. The study further suggests that the normal pulmonary vasodilatation seen on exercise is not mediated pharmacologically, but is a secondary consequence to the mechanical effects of a rise in pulmonary blood flow. This study thus supports the view that there is no resting vasoconstrictor tone in the pulmonary vascular bed.

scholarly journals Usage of Inhaled Nitric Oxides in Cases of Eisenmenger Syndrome

2020 ◽  
Vol 1 (1) ◽  
pp. 13-19
Author(s):  
Nenny Triastuti ◽  
Muhammad Perdana Airlangga ◽  
Muhammad Anas
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Vascular Tissue ◽  
Inhaled Nitric Oxide ◽  
Nitric Oxides ◽  
Eisenmenger Syndrome ◽  
Pulmonary Vasodilation ◽  
High Concentrations ◽  
The Right ◽  
Nitric Oxide Therapy

Eisenmenger Syndrome is congenital heart disease with pulmonary hypertension and shunting turning from right to left. The resistance of pulmonary vascular more than 7.5 mmHg/L/min. The right ventricle and pulmonary artery always enlarge. Physiological effects of inhaled nitric oxide therapy cause selective pulmonary vasodilation: Hypoxia alveoli causes reversible vasoconstriction, thereby increasing pulmonary wedge pressure. Inhaled nitric oxide can lower it. Moderate cardiac output and systematic arterial pressure are not affected; Selective in pulmonary because it is activated by hemoglobin; Selective vasodilation in the ventilated area, local hypoxia alveoli constricts the surrounding vascular tissue and redistributes blood flow to the ventilated lungs better and higher intraalveolar oxygen pressure. Inhaled nitric oxide enhances this mechanism by increasing blood flow through a well-ventilated lung; Bronchodilators; Pulmonary surfactant, The combination of high concentrations of inspired oxygen and high concentrations of Inhaled nitric oxide reduces the minimum surfactant surface tension.

scholarly journals Neonatal platelet count trends during inhaled nitric oxide therapy

2019 ◽  
Author(s):  
Christopher S Thom ◽  
Matthew Devine ◽  
Stacey Kleinman ◽  
Erik A Jensen ◽  
Michele P Lambert ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Platelet Count ◽  
Lung Injury ◽  
Lung Tissue ◽  
Inhaled Nitric Oxide ◽  
Pulmonary Vasodilation ◽  
Recent Debate ◽  
Clinically Significant ◽  
Nitric Oxide Therapy

AbstractRecent debate has focused on the significance of platelets generated in lung tissue. Here, we retrospectively analyzed platelet count changes in neonates requiring inhaled nitric oxide (iNO) pulmonary vasodilation therapy for pulmonary hypertension. There were no clinically significant changes in platelet count upon iNO initiation or during iNO therapy. Unexpectedly, platelet counts increased after iNO cessation. These findings argue against a clinically meaningful untapped pulmonary repository of megakaryocytes and platelets in this context, although acute platelet count increases might be expected after discontinuing iNO in some patients. Further work is needed to clarify the underlying etiology for these observations, and to better delineate the mechanisms for platelet count increases after recovery from lung injury.

Disruption of renal peritubular blood flow in lipopolysaccharide-induced renal failure: role of nitric oxide and caspases

2005 ◽  
Vol 289 (6) ◽  
pp. F1324-F1332 ◽  
Author(s):  
Manish M. Tiwari ◽  
Robert W. Brock ◽  
Judit K. Megyesi ◽  
Gur P. Kaushal ◽  
Philip R. Mayeux
Keyword(s):  
Nitric Oxide ◽  
Renal Failure ◽  
Blood Flow ◽  
Saline Group ◽  
No Production ◽  
Capillary Perfusion ◽  
Peritubular Capillary ◽  
Synthase Inhibitor ◽  
Peritubular Capillary Perfusion

Acute renal failure (ARF) is a frequent and serious complication of endotoxemia caused by lipopolysaccharide (LPS) and contributes significantly to mortality. The present studies were undertaken to examine the roles of nitric oxide (NO) and caspase activation on renal peritubular blood flow and apoptosis in a murine model of LPS-induced ARF. Male C57BL/6 mice treated with LPS ( Escherichia coli) at a dose of 10 mg/kg developed ARF at 18 h. Renal failure was associated with a significant decrease in peritubular capillary perfusion. Vessels with no flow increased from 7 ± 3% in the saline group to 30 ± 4% in the LPS group ( P < 0.01). Both the inducible NO synthase inhibitor l- N6-1-iminoethyl-lysine (l-NIL) and the nonselective caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (Z-VAD) prevented renal failure and reversed perfusion deficits. Renal failure was also associated with an increase in renal caspase-3 activity and an increase in renal apoptosis. Both l-NIL and Z-VAD prevented these changes. LPS caused an increase in NO production that was blocked by l-NIL but not by Z-VAD. Taken together, these data suggest NO-mediated activation of renal caspases and the resulting disruption in peritubular blood flow are an important mechanism of LPS-induced ARF.

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