Role of endothelium-derived relaxing factor during transition of pulmonary circulation at birth

Abman, Steven H.; Chatfield, Barbara A.; Hall, S. L.; McMurtry, Ivan F.

doi:10.1152/ajpheart.1990.259.6.h1921

Cited by 284 publications

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“…First, in fetal lambs, acetylcholine decreases pulmonary vascular resistance and increases pulmonary blood flow (41); these hemodynamic effects are blocked by N -nitro-l-arginine or other l-arginine analogs which inhibit NO synthesis (41). Second, inhibition of NO synthesis increases pulmonary vascular resistance in fetal lambs and attenuates the increase in pulmonary blood flow induced by maternal hyperbaric oxygen exposure, ventilation with air or oxygen (8)(9)(10)16), or compression of the ductus arteriosus. Third, l-arginine, the precursor of NO, increases pulmonary blood flow in fetal and newborn lambs and augments endothelium-dependent pulmonary vasodilation (8, Figure 2.…”

Section: Discussionmentioning

confidence: 99%

“…The increase in alveolar or pulmonary and systemic arterial blood oxygen tensions decreases pulmonary vascular resistance either directly by dilating the small pulmonary arteries, or indirectly by stimulating the production of vasodilator substances such as nitric oxide (NO) 1 (8)(9)(10). Endothelial cells synthesize NO and l -citrulline from l -arginine by the action of the enzyme endothelial nitric oxide synthase (eNOS) (11,12).…”

Section: Introductionmentioning

confidence: 99%

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Ventilation and oxygenation induce endothelial nitric oxide synthase gene expression in the lungs of fetal lambs.

Black¹,

Johengen²,

Dong³

et al. 1997

J. Clin. Invest.

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At birth, ventilation and oxygenation immediately decrease pulmonary vascular resistance (PVR) and increase pulmonary blood flow (PBF); more gradual changes occur over the next several hours. Nitric oxide, produced by endothelial nitric oxide synthase (eNOS), mediates these gradual changes. To determine how ventilation and oxygenation affect eNOS gene expression, 12 fetal lambs were ventilated for 8 h without changing fetal descending aortic blood gases or pH (rhythmic distension) or with 100% oxygen (O 2 ventilation). Vascular pressures and PBF were measured. Total RNA, protein, and tissue sections were prepared from lung tissue for RNase protection assays, Western blotting, and in situ hybridization. O 2 ventilation increased PBF and decreased PVR more than rhythmic distension ( P Ͻ 0.05). Rhythmic distension increased eNOS mRNA expression; O 2 ventilation increased eNOS mRNA expression more and increased eNOS protein expression ( P Ͻ 0.05). To define the mechanisms responsible for these changes, ovine fetal pulmonary arterial endothelial cells were exposed to 1, 21, or 95% O 2 or to shear stress. 95% O 2 increased eNOS mRNA and protein expression ( P Ͻ 0.05). Shear stress increased eNOS mRNA and protein expression ( P Ͻ 0.05). Increased oxygenation but more importantly increased PBF with increased shear stress induce eNOS gene expression and contribute to pulmonary vasodilation after birth. (

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ventilation and oxygenation induce endothelial nitric oxide synthase gene expression in the lungs of fetal lambs.

Black¹,

Johengen²,

Dong³

et al. 1997

J. Clin. Invest.

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“…Arterial blood gases were monitored frequently (every 5-15 min) during initial stabilization. Ventilator settings (PIP and rate) were adjusted to maintain arterial PCO 2 Figure 1.…”

Section: Methodsmentioning

confidence: 99%

“…Oxygen plays a crucial role in mediating pulmonary vascular transition at birth and even small increases in fetal oxygenation (similar to or less than that induced by room air ventilation) result in a dramatic decrease in pulmonary vascular resistance (1)(2)(3). However, the debate regarding the use of oxygen for neonatal resuscitation has intensified in recent years.…”

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confidence: 99%

Pulmonary Arterial Contractility in Neonatal Lambs Increases with 100% Oxygen Resuscitation

et al. 2006

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ABSTRACT:The optimal FiO 2 during neonatal resuscitation is a subject of controversy. The effect of exposure to high levels of inspired oxygen on pulmonary arterial (PA) contractility is not known. We studied differences in PA vasoreactivity in term lambs initially ventilated with 21% or 100% oxygen, followed by continued ventilation using oxygen as needed for 24 h, or ventilated with 100% oxygen for 24 h and room air breathing 1-d-old lambs. Term lambs were delivered by cesarean section, intubated, and ventilated with 21% (21%Res) or 100% oxygen (100%Res) for the first 30 min of life. Subsequently, the ventilator FiO 2 was adjusted to maintain a PaO 2 between 45 and 65 mm Hg for 24 h. Five lambs were ventilated continuously with 100% oxygen (100%24h). Six spontaneously breathing newborn lambs (RA Spont) were studied for comparison. Lambs were killed at 24 h of life and PA rings were isolated and contracted with norepinephrine (NE) and KCl and some were relaxed with A23187 and SNAP in tissue baths. NE and KCl induced contractions were highest in PA isolated from 100%24h lambs, and were significantly higher in 100%Res lambs than PA from 21%Res lambs. Contraction responses in PA from RA Spont lambs were similar to 21%Res lambs. Relaxations to A23187 and SNAP were similar among all ventilated groups. PA contractility to NE and KCl is increased following both brief (30 min) and prolonged (24 h) exposure to 100% oxygen during mechanical ventilation. In contrast, normoxic resuscitation and ventilation do not increase PA contractility. T he extent of oxygen supplementation during optimal resuscitation of a newborn infant remains controversial. Oxygen plays a crucial role in mediating pulmonary vascular transition at birth and even small increases in fetal oxygenation (similar to or less than that induced by room air ventilation) result in a dramatic decrease in pulmonary vascular resistance (1-3). However, the debate regarding the use of oxygen for neonatal resuscitation has intensified in recent years. New arguments have been added to the debate as more and more data indicate that not only is room air as good as 100% oxygen for resuscitation but that even a brief exposure to pure oxygen at birth might be detrimental (4). It has been suggested that breathing 100% oxygen dilates constricted pulmonary arteries more efficiently than room air. However, ultrasound and direct estimation of pulmonary arterial pressure in asphyxiated piglets demonstrated that pulmonary hypertension normalized as quickly with room air as with 100% oxygen (5,6).NE constriction of pulmonary arteries isolated from fetal and neonatal animals after normal transition has been studied in detail (7-9). However, the effect of oxygen exposure during resuscitation and or ventilation on the contractile response to NE is not known.We hypothesized that exposure to 100% oxygen during resuscitation would result in formation of reactive oxygen species and induce increased pulmonary arterial contractile response and that the increased contractility would be prop...

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“…The factors accounting for maintenance of high pulmonary vascular resistance prenatally and its rapid decrease after birth are not completely understood. Pulmonary vascular nitric oxide (NO) availability and its relaxant effect on smooth muscle are considered to play an important role in the transition from fetal to neonatal circulation (1).…”

mentioning

confidence: 99%

Developmental changes in arginase expression and activity in the lung

Belik

Shehnaz²,

Pan³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Arginases compete with nitric oxide (NO) synthases for L-arginine as common substrate. Pulmonary vascular and airway diseases in which arginase activity is increased are associated with decreased NO production and reduced smooth muscle relaxation. The developmental patterns of arginase activity and type I and II isoforms expression in the lung have not been previously evaluated. Hypothesizing that lung arginase activity is developmentally regulated and highest in the fetus, we measured the expression of both arginase isoforms and total arginase activity in fetal, newborn, and adult rat lung, pulmonary artery, and bronchial tissue. In addition, intrapulmonary arterial muscle force generation was evaluated in the absence and presence of the arginase inhibitor N -hydroxy-nor-L-arginine (nor-NOHA). Arginase II content, as well as total arginase activity, was highest in fetal rat lung, bronchi, and pulmonary arterial tissue and decreased with age (P Ͻ 0.05), and its lung cell expression was developmentally regulated. In the presence of nor-NOHA, pulmonary arterial force generation was significantly reduced in fetus and newborn (P Ͻ 0.01). No significant change in force generation was noted in bronchial tissue following arginase inhibition. In conclusion, arginase II is regulated developmentally, and both expression and activity are maximal during fetal life. We speculate that the maintenance of a high pulmonary vascular resistance and decreased lung NO production prenatally may, in part, be dependent on increased arginase expression and/or activity. pulmonary vascular resistance; airway resistance; nitric oxide GIVEN THE HIGH FETAL PULMONARY vascular resistance, pulmonary blood flow prenatally is less than 10% of the total cardiac output. Pulmonary vascular resistance rapidly decreases at birth and reaches the low physiological level of adults at the end of the neonatal period (12). The factors accounting for maintenance of high pulmonary vascular resistance prenatally and its rapid decrease after birth are not completely understood. Pulmonary vascular nitric oxide (NO) availability and its relaxant effect on smooth muscle are considered to play an important role in the transition from fetal to neonatal circulation (1).NO is produced by nitric oxide synthases (NOS). In the lung, three NOS isoforms are present. Endothelial NOS (eNOS) is expressed in pulmonary vascular endothelium and bronchial epithelium, whereas neuronal (nNOS) and inducible (iNOS)

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Role of endothelium-derived relaxing factor during transition of pulmonary circulation at birth

Cited by 284 publications

References 0 publications

Ventilation and oxygenation induce endothelial nitric oxide synthase gene expression in the lungs of fetal lambs.

Ventilation and oxygenation induce endothelial nitric oxide synthase gene expression in the lungs of fetal lambs.

Pulmonary Arterial Contractility in Neonatal Lambs Increases with 100% Oxygen Resuscitation

Developmental changes in arginase expression and activity in the lung

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