Pulmonary Neuroepithelial Bodies in Neonatal Rats Chronically Exposed to Nitric Oxide

2000 ◽  
Vol 6 (S2) ◽  
pp. 880-881
Author(s):  
Kuen-Shan Hung ◽  
Xay K. Her
Keyword(s):  
Nitric Oxide ◽  
Endocrine Cells ◽  
Pediatric Patients ◽  
Chronic Hypoxia ◽  
Gas Sensing ◽  
Ductus Arteriosus ◽  
Neuroepithelial Bodies ◽  
Pulmonary Vasoconstriction ◽  
Neonatal Lungs ◽  
Inhaled No

Pulmonary neuroepithelial bodies (NEBs) consist of clusters of innervated endocrine cells localized in human and animal lungs. They are prominent in late fetal and neonatal lungs and their density declines with increased postnatal age. Gas sensing functions of these structures have been suggested by Lauweryns and Cokelaere. Subsequent experiments show that chronic hypoxia leads to an increase in the size or number of NEBs, and prolonged hyperoxia also causes elevation of NEB numbers. Animals exposed to cigarette smoke also had an increased number of immunoreactive NEBs.Inhaled nitric oxide (NO) can reverse pulmonary vasoconstriction induced by hypoxic breathing or ligation of ductus arteriosus in newborn and young animals. These studies led to clinical use of NO for treatment of pediatric patients with pulmonary hypertension. However, direct effects of inhaled NO on various components of the lung are not clearly understood.

Helium inhalation enhances vasodilator effect of inhaled nitric oxide on pulmonary vessels in hypoxic dogs

2001 ◽  
Vol 280 (4) ◽  
pp. H1875-H1881 ◽  
Author(s):  
Masaki Nie ◽  
Hirosuke Kobayashi ◽  
Motoaki Sugawara ◽  
Tomoyuki Tomita ◽  
Kuniyoshi Ohara ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Artery ◽  
Characteristic Impedance ◽  
Gas Mixture ◽  
Facilitated Diffusion ◽  
Hemodynamic Parameters ◽  
Pulmonary Vasoconstriction ◽  
Vasodilatory Effect ◽  
Pulmonary Hemodynamic ◽  
Inhaled No

There are theoretical and experimental indications that the presence of He as a balance gas markedly increase the diffusion velocity of other gases contained in a gas mixture. We allowed dogs with pulmonary vasoconstriction induced by hypoxia to inhale a mixture of 5 parts per million (ppm) of nitric oxide (NO) and O2 balanced with He (NO in He) instead of N2 (NO in N2). The dilating effect of NO in He and NO in N2 on the pulmonary artery was evaluated by determining conventional pulmonary hemodynamic parameters, mean pulmonary artery (PA) pressure (MPAP), and pulmonary vascular resistance indexed to body surface area (PVRI), pulmonary impedance ( Z), and the recently developed hemodynamic index, time-corrected wave intensity (WI). The main findings in this study were as follows: 1) hypoxia increased MPAP, PVRI, Z at 0 Hz ( Z 0), Z at the first harmonics, characteristic impedance ( Z c), the reflection coefficient (Γ), and the first peak of WI; 2) NO in N2 reduced Z 0and Γ; and 3) NO in He reduced the first peak of WI and reduced Z 0 and Γ more than NO in N2. The enhanced vasodilatory effect of NO in He might be associated with facilitated diffusion of NO diluted in the gas mixture with He. In conclusion, increased efficacy of NO in He offers the possibility to reduce the inhaled NO concentration.

Improvement in Oxygenation by Phenylephrine and Nitric Oxide in Patients with Adult Respiratory Distress Syndrome 

1997 ◽  
Vol 87 (1) ◽  
pp. 18-25 ◽  
Author(s):  
Elana B. Doering ◽  
C. William Hanson ◽  
Daniel J. Reily ◽  
Carol Marshall ◽  
Bryan E. Marshall
Keyword(s):  
Nitric Oxide ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Adult Respiratory Distress Syndrome ◽  
Distress Syndrome ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Random Order ◽  
Pulmonary Vasoconstriction ◽  
Arterial Blood ◽  
Inhaled No

Background Inhaled nitric oxide (NO), a selective vasodilator, improves oxygenation in many patients with adult respiratory distress syndrome (ARDS). Vasoconstrictors may also improve oxygenation, possibly by enhancing hypoxic pulmonary vasoconstriction. This study compared the effects of phenylephrine, NO, and their combination in patients with ARDS. Methods Twelve patients with ARDS (PaO2/FIO2 <le> 180; Murray score <me> 2) were studied. Each patient received three treatments in random order: intravenous phenylephrine, 50-200 micrograms/min, titrated to a 20% increase in mean arterial blood pressure; inhaled NO, 40 ppm; and the combination (phenylephrine+NO). Hemodynamics and blood gas measurements were made during each treatment and at pre- and posttreatment baselines. Results All three treatments improved PaO2 overall. Six patients were "phenylephrine-responders" (delta PaO2 > 10 mmHg), and six were "phenylephrine-nonresponders." In phenylephrine-responders, the effect of phenylephrine was comparable with that of NO (PaO2 from 105 +/- 14 to 132 +/- 14 mmHg with phenylephrine, and from 110 +/- 14 to 143 +/- 19 mmHg with NO), and the effect of phenylephrine+NO was greater than that of either treatment alone (PaO2 from 123 +/- 13 to 178 +/- 23 mmHg). In phenylephrine-nonresponders, phenylephrine did not affect PaO2, and the effect of phenylephrine+NO was not statistically different from that of NO alone (PaO2 from 82 +/- 12 to 138 +/- 28 mmHg with NO; from 84 +/- 12 to 127 +/- 23 mmHg with phenylephrine+NO). Data are mean +/- SEM. Conclusions Phenylephrine alone can improve PaO2 in patients with ARDS. In phenylephrine-responsive patients, phenylephrine augments the improvement in PaO2 seen with inhaled NO. These results may reflect selective enhancement of hypoxic pulmonary vasoconstriction by phenylephrine, which complements selective vasodilation by NO.

Site of pulmonary vasodilation by inhaled nitric oxide in the perfused lung

1995 ◽  
Vol 78 (5) ◽  
pp. 1745-1749 ◽  
Author(s):  
S. Rimar ◽  
C. N. Gillis
Keyword(s):  
Nitric Oxide ◽  
Vascular Occlusion ◽  
Inhaled Nitric Oxide ◽  
Krebs Solution ◽  
Total Resistance ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasoconstriction ◽  
Perfused Lung ◽  
Occlusion Technique ◽  
Inhaled No

To determine the site of inhaled nitric oxide (NO)-induced pulmonary vasodilation, a double vascular occlusion technique was used with rabbit lungs ventilated and perfused at 20 ml/min with Krebs solution containing 3% dextran and 30 microM indomethacin. Inhaled NO (120 ppm for 3 min) reduced pulmonary vasoconstriction produced by U-46619 infusion (0.5–1.2 nmol/min), significantly decreasing total resistance (RT) [1,080 +/- 51 (SE) vs. 1,545 +/- 109 mmHg.l–1.min; P < 0.01]. Acetylcholine infusion (ACh; 2–5 nmol/min) and nitroglycerin (NTG; 0.35 mumol) likewise decreased RT. Arterial resistance (Ra) was also significantly less with inhaled NO, ACh, and NTG compared with U-46619 alone. Venous resistance (Rv), however, was unchanged. When the direction of perfusion was reversed in the lung, inhaled NO, ACh, and NTG significantly decreased RT compared with U-46619 alone, and Rv was also reduced by all three agents. After electrolysis-induced acute lung injury, inhaled NO significantly reduced both RT and Ra compared with U-46619 alone, whereas Rv was unaffected. Our results demonstrate that inhaled NO gas affects primarily the arterial (precapillary) component of the pulmonary circulation but, under conditions of extreme venous constriction, may dilate the postcapillary component as well.

Nitric oxide inhalation: effects on the ovine neonatal pulmonary and systemic circulations

1996 ◽  
Vol 8 (3) ◽  
pp. 431 ◽  
Author(s):  
V DeMarco ◽  
JW Skimming ◽  
TM Ellis ◽  
S Cassin
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Arterial Pressure ◽  
Pulmonary Circulation ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Minimum Concentration ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial ◽  
Inhaled No

Others have shown that inhaled nitric oxide causes reversal of pulmonary hypertension in anaesthetized perinatal sheep. The present study examined haemodynamic responses to inhaled NO in the normal and constricted pulmonary circulation of unanaesthetized newborn lambs. Three experiments were conducted on each of 7 lambs. First, to determine a minimum concentration of NO which could reverse acute pulmonary hypertension caused by infusion of the thromboxame mimic U46619, the haemodynamic effects of 5 different doses of inhaled NO were examined. Second, the effects of inhaling 80 ppm NO during hypoxic pulmonary vasoconstriction were examined. Finally, to determine if tachyphalaxis occurs during NO inhalation, lambs were exposed to 80 ppm NO for 3 h during which time pulmonary arterial pressure was doubled by infusion of U46619. Breathing NO (80 ppm) caused a slight but significant decrease in pulmonary vascular resistance (PVR) in lambs with normal pulmonary arterial pressure (PAP). Nitric oxide, inhaled at concentrations between 10 and 80 ppm for 6 min (F1O2 = 0.60), caused decreases in PVR when PAP was elevated with U46619. Nitric oxide acted selectively on the pulmonary circulation, i.e. no changes occurred in systemic arterial pressure or any other measured variable. Breathing 80 ppm NO for 6 min reversed hypoxic pulmonary vasoconstriction. In the chronic exposure study, inhaling 80 ppm NO for 3 h completely reversed U46619-induced pulmonary hypertension. Although arterial methaemoglobin increased during the 3-h exposure to 80 ppm NO, there was no indication that this concentration of NO impairs oxygen loading. These data demonstrate that NO, at concentrations as low as 10 ppm, is a potent, rapid-action, and selective pulmonary vasodilator in unanaesthetized newborn lambs with elevated pulmonary tone. Furthermore, these data support the use of inhaled NO for treatment of infants with pulmonary hypertension.

Inhaled nitric oxide reverses hypoxic pulmonary vasoconstriction without impairing gas exchange

1993 ◽  
Vol 74 (3) ◽  
pp. 1287-1292 ◽  
Author(s):  
U. Pison ◽  
F. A. Lopez ◽  
C. F. Heidelmeyer ◽  
R. Rossaint ◽  
K. J. Falke
Keyword(s):  
Nitric Oxide ◽  
Gas Exchange ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Blood Gas Analysis ◽  
Gas Analysis ◽  
Pulmonary Gas Exchange ◽  
Blood Gas ◽  
Hemodynamic Effects ◽  
Pulmonary Vasoconstriction ◽  
Inhaled No

Nitric oxide (NO) is an endogenous endothelium-derived relaxing factor that participates in the regulation of vascular tone. We studied the effects of inhaled NO gas on transient hypoxic pulmonary vasoconstriction and normal lungs in mechanically ventilated sheep. We measured hemodynamics and pulmonary gas exchange. For gas exchange measurements we used conventional blood gas analysis and the multiple inert gas elimination technique to estimate ventilation-perfusion heterogeneity. Our hypotheses were 1) inhaled NO reverses hypoxic pulmonary vasoconstriction, 2) the hemodynamic effects of inhaled NO are limited to the pulmonary circulation, and 3) inhaled NO does not impair pulmonary gas exchange and may redistribute blood flow to better ventilated areas of the lungs. Hypoxic pulmonary vasoconstriction was induced by using a hypoxic inspiratory gas mixture. The addition of 20 ppm NO to the hypoxic inspiratory gases returned pulmonary arterial pressure to baseline values. Systemic hemodynamics and gas exchange indexes derived from conventional blood gas analysis remained constant. Gas exchange indexes for ventilation-perfusion ratios and gas dispersions improved. The addition of 20 ppm NO to medical air (21% O2) had no such significant effects on hemodynamics or pulmonary gas exchange. Our findings show that inhaled NO reverses transient hypoxic pulmonary vasoconstriction. The hemodynamic effects of NO are limited to the pulmonary circulation; it does not impair pulmonary gas exchange. Moreover, it redistributes blood flow to better ventilated alveoli. As such, NO has potential in the treatment of lung diseases associated with pulmonary hypertension.

Nitric oxide and nitroglycerin reversal of pulmonary vasoconstriction induced by alpha-activation during exercise

1996 ◽  
Vol 270 (3) ◽  
pp. H875-H880
Author(s):  
T. Koizumi ◽  
C. I. Hermo ◽  
L. J. Bjertnaes ◽  
M. Banerjee ◽  
J. H. Newman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Beta Blockade ◽  
Second Phase ◽  
Adrenergic Blockade ◽  
Intravenous Nitroglycerin ◽  
Pulmonary Vasoconstriction ◽  
Inhaled No ◽  
Control Exercise

We have previously shown in sheep that pulmonary vascular resistance decreases rapidly after the onset of constant exercise, followed by a slower and smaller second vasodilation. The second phase is partly regulated by alpha- and beta-adrenoceptor activation. We examined the effect of inhaled nitric oxide (NO; 40 ppm) and intravenous nitroglycerin on beta-adrenergic blockade-induced pulmonary vasoconstriction during exercise. In paired studies, we exercised eight sheep at a constant rate of 4 miles per hour for 4 min on a treadmill and measured the hemodynamic response during beta-blockade (propranolol, 1 mg i.v.) with and without 40 ppm inhaled NO or continuous infusion of nitroglycerin (3.2-4.0 micrograms.kg-1.min-1). beta-Blockade resulted in a higher pulmonary vascular resistance during steady-state exercise (40-240 s) than in the unblocked state; reduction in pulmonary vascular resistance during the second phase of exercise was smaller with beta-blockade (13-16%) than with control exercise (26-30%). Inhaled NO and nitroglycerin reversed the beta-blockade-related pulmonary vasoconstriction to the levels of control exercise. Inhaled NO and intravenous nitroglycerin also reversed the pulmonary vasoconstriction produced by intravenous phenylephrine at rest. We conclude that exogenous NO, delivered by gas inhalation or via nitroso compounds, opposes and fully reverses alpha-receptor-activated pulmonary vasoconstriction during exercise in sheep.

Pulmonary vasodilation by inhaled nitric oxide after endothelial injury

1992 ◽  
Vol 73 (5) ◽  
pp. 2179-2183 ◽  
Author(s):  
S. Rimar ◽  
C. N. Gillis
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Free Radical ◽  
Perfusion Pressure ◽  
Inhaled Nitric Oxide ◽  
Arterial Perfusion ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial ◽  
Inhaled No

Inhaled nitric oxide gas (NO) has recently been shown to reverse experimentally induced pulmonary vasoconstriction. To examine the effect of free radical injury and methylene blue exposure on inhaled NO-induced pulmonary vasodilation we studied ventilated rabbit lungs perfused with Krebs solution containing 3% dextran and indomethacin. When NO gas (120 ppm) was added to the inhaled mixture for 3 min, the elevated pulmonary arterial perfusion pressure (Ppa) induced by the thromboxane analogue U-46619 was significantly reduced [8 +/- 2 (SE) mmHg]. Acetylcholine similarly reduced Ppa (9 +/- 1 mmHg). After free radical injury and methylene blue exposure, inhaled NO again produced significant vasodilation (5 +/- 1 and 9 +/- 2 mmHg, respectively), but acetylcholine resulted in an increase in Ppa (-9 +/- 3 and -4 +/- 1 mmHg, respectively). These data demonstrate that pulmonary vasodilation produced by inhaled NO is unaffected by free radical injury or methylene blue in the intact lung despite concomitant reversal of acetylcholine-induced vasodilation.

Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibition of Rho-kinase

2004 ◽  
Vol 287 (4) ◽  
pp. L656-L664 ◽  
Author(s):  
Karen A. Fagan ◽  
Masahiko Oka ◽  
Natalie R. Bauer ◽  
Sarah A. Gebb ◽  
D. Dunbar Ivy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Pulmonary Circulation ◽  
Vascular Remodeling ◽  
Chronic Hypoxia ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Rho Kinase ◽  
Hypoxic Pulmonary Hypertension ◽  
Pulmonary Vasoconstriction

RhoA GTPase mediates a variety of cellular responses, including activation of the contractile apparatus, growth, and gene expression. Acute hypoxia activates RhoA and, in turn, its downstream effector, Rho-kinase, and previous studies in rats have suggested a role for Rho/Rho-kinase signaling in both acute and chronically hypoxic pulmonary vasoconstriction. We therefore hypothesized that activation of Rho/Rho-kinase in the pulmonary circulation of mice contributes to acute hypoxic pulmonary vasoconstriction and chronic hypoxia-induced pulmonary hypertension and vascular remodeling. In isolated, salt solution-perfused mouse lungs, acute administration of the Rho-kinase inhibitor Y-27632 (1 × 10−5 M) attenuated hypoxic vasoconstriction as well as that due to angiotensin II and KCl. Chronic treatment with Y-27632 (30 mg·kg−1·day−1) via subcutaneous osmotic pump decreased right ventricular systolic pressure, right ventricular hypertrophy, and neomuscularization of the distal pulmonary vasculature in mice exposed to hypobaric hypoxia for 14 days. Analysis of a small number of proximal pulmonary arteries suggested that Y-27632 treatment reduced the level of phospho-CPI-17, a Rho-kinase target, in hypoxic lungs. We also found that endothelial nitric oxide synthase protein in hypoxic lungs was augmented by Y-27632, suggesting that enhanced nitric oxide production might have played a role in the Y-27632-induced attenuation of chronically hypoxic pulmonary hypertension. In conclusion, Rho/Rho-kinase activation is important in the effects of both acute and chronic hypoxia on the pulmonary circulation of mice, possibly by contributing to both vasoconstriction and vascular remodeling.

Chronic inhaled nitric oxide: effects on pulmonary vascular endothelial function and pathology in rats

1996 ◽  
Vol 80 (1) ◽  
pp. 252-260 ◽  
Author(s):  
C. M. Roos ◽  
D. U. Frank ◽  
C. Xue ◽  
R. A. Johns ◽  
G. F. Rich
Keyword(s):  
Nitric Oxide ◽  
Vascular Remodeling ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Muscle Thickness ◽  
Pulmonary Vascular Remodeling ◽  
Normobaric Oxygen ◽  
Hypoxic Conditions ◽  
The Right ◽  
Inhaled No

Nitric oxide (NO) is a potent endogenous vasodilator produced in endothelial cells. Inhaled NO selectively vasodilates the pulmonary circulation. We determined the effects of chronic inhaled NO on hypoxic pulmonary vascular remodeling and endothelium NO-dependent and -independent vasodilation during normoxic and hypoxic conditions in rats. Rats were exposed to 3 wk of normoxia (N), normoxia + 20 ppm inhaled NO (N+NO), chronic hypoxia with 10% normobaric oxygen (CH), or CH and 20 ppm inhaled NO (CH+NO). Inhaled NO decreased the number of muscular pulmonary arteries, the medial smooth muscle thickness, and the right ventricular hypertrophy associated with chronic hypoxia but had no effect on these parameters in normoxic rats. All groups were evaluated with isolated perfused lungs. The pulmonary artery pressure increased by the same amount in the CH and CH+NO rats compared with N rats. Inhibition of NO synthase with N omega-nitro-L-arginine methyl ester (L-NAME) caused greater pulmonary vasoconstriction in CH (19.2 +/- 3.7 mmHg) vs. N (7.8 +/- 3.0 mmHg) and less in CH+NO (9.1 +/- 0.8 mmHg) vs. CH rats. Bradykinin (3 micrograms) caused greater vasodilation in CH (76 +/- 12%) vs. N (29 +/- 5%) but significantly less in CH+NO (41 +/- 11%) vs. CH rats. Vasodilation with acute inhaled NO (40 ppm) was no different in CH vs. N rats but was lower in CH+NO (19 +/- 5%) vs. CH (34 +/- 6%) rats. This study demonstrates that chronic inhaled NO attenuates hypoxic pulmonary vascular remodeling. Furthermore, these results suggest that chronic inhaled NO decreases endothelium NO-dependent and -independent vasodilation.

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