Endogenous nitric oxide modulates responses of tissue  and airway resistance to vagal stimulation in piglets

Khassawneh, Mohammad; Dreshaj, Ismail A.; Liu, Shijian; Chang, Chung Ho; Haxhiu, Musa A.; Martin, Richard J.

doi:10.1152/japplphysiol.01078.2001

Cited by 18 publications

(14 citation statements)

References 36 publications

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“…These findings for pulmonary function are consistent with the known role of NO in the regulation of both bronchomotor tone and peripheral contractile elements in the developing lung (40). We were surprised to find no positive association of in vitro surfactant function with parameters of lung function as observed in adult patients with idiopathic pulmonary fibrosis (29).…”

supporting

confidence: 81%

Surfactant Composition and Function in a Primate Model of Infant Chronic Lung Disease: Effects of Inhaled Nitric Oxide

et al. 2006

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Bronchopulmonary dysplasia, or chronic lung disease (CLD), of premature infants involves injury from hyperoxia and mechanical ventilation to an immature lung. We examined surfactant and nitric oxide (NO), which are developmentally deficient in premature infants, in the baboon model of developing CLD. Fetuses were delivered at 125 d gestation and were managed for 14 d with ventilation and oxygen prn without (controls) or with inhaled NO at 5 ppm. Compared with term infants, premature control infants had reduced maximal lung volume, decreased tissue content of surfactant proteins SP-A, -B, and -C, abnormal lavage surfactant as assessed by pulsating bubble surfactometer, and a low concentration of SP-B/ phospholipid. NO treatment significantly increased maximal lung volume and tissue SP-A and SP-C, reduced recovery of lavage surfactant by 33%, decreased the total protein:phospholipid ratio of surfactant by 50%, and had no effect on phospholipid composition or SP content except for SP-C (50%). In both treatment groups, levels of SP-B and SP-C in surfactant were negatively correlated with STmin, with a 5-fold greater SP efficiency for NO versus control animals. By contrast, lung volume and compliance were not correlated with surfactant function. We conclude that surfactant is often dysfunctional in developing CLD secondary to SP-B deficiency. NO treatment improves the apparent ability of hydrophobic SP to promote low surface tension, perhaps secondary to less protein inactivation of surfactant, and improves lung volume by a process unrelated to surfactant function. (Pediatr Res 59: 157-163, 2006) B PD is a common and serious condition among premature infants. The pathogenesis involves interrupted lung development and interstitial fibrosis secondary to oxygen, ventilator treatment, inflammation, and infection imposed upon an immature lung. Infants with severe BPD have continuing oxygen and ventilator requirement that is often complicated by increased pulmonary vascular and airway resistance (1).Most premature infants are developmentally deficient in pulmonary surfactant, the complex mixture of PL and SP that is required for maintaining alveolar patency (2). In addition, the composition of surfactant at premature birth is abnormal, with a relative deficiency of both saturated phosphatidylcholine, which forms the surface active film, and SP that are essential for formation and stability of film (3,4). Many premature infants who remain on ventilatory support experience episodes of respiratory deteriorations that are associated with dysfunctional surfactant and a reduced concentration of SP-B and SP-C (5).The signaling molecule NO plays a key role in physiologic processes in the pulmonary epithelium, mediating neurotransmission, smooth muscle relaxation, bacteriostasis, ciliary motility, mucin secretion, and lung liquid production in the perinatal period (6,7). We previously reported that there are maturational increases in NO synthases and NO production, and that NO synthases are deficient in baboon infants wit...

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supporting

confidence: 81%

Surfactant Composition and Function in a Primate Model of Infant Chronic Lung Disease: Effects of Inhaled Nitric Oxide

et al. 2006

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“…Moreover, the potent NO synthase (NOS) inhibitor N G -nitro- L -arginine methyl ester ( L -NAME) has been found, as expected, to induce an increase in airway resistance in guinea pigs [7,8] and pigs [9,10], but this finding was not confirmed in rats [11] or in humans [12]. …”

Section: Introductionmentioning

confidence: 99%

The Effect of N<sup>G</sup>-Nitro-<i>L</i>-Arginine Methyl Ester, a Nitric Oxide Synthase Inhibitor, on Respiratory Mechanics in Rats

Rubini

2011

Respiration

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Background: Data describing the inhibitory effects of nitric oxide synthase (NOS) on respiratory mechanics are conflicting, and no data are available concerning possible effects on the viscoelasticity of the respiratory system, on the inspiratory work of breathing (WOB) or on respiratory system hysteresis. Objectives: The aim of this study was to measure the effects of NOS inhibition by N^G-nitro-L-arginine methyl ester (L-NAME) on respiratory mechanics in normal anesthetized rats. Methods: Using the end-inflation occlusion method, it was possible to quantify the ohmic and viscoelastic airway resistance and elastance of the respiratory system. Ohmic resistance is the normalized-to-flow pressure dissipation due to viscous forces opposing the airflow in the airways, as predicted by the Poiseuille law. Viscoelastic resistance is the normalized-to-flow pressure dissipation due to the resistance of respiratory system tissue to deformation during inflation, which is recovered after the arrest of the inspiratory flow (stress relaxation). The inspiratory WOB, its elastic and resistive components, and hysteresis were also calculated. Results:L-NAME induced an increment in the ohmic airway resistance and in the resistive ohmic inspiratory WOB. The viscoelastic resistance due to stress relaxation and the elastic properties of the respiratory system were not modified, and no effect was detected on the related components of the inspiratory WOB and on hysteresis. Conclusions: NO acts in normal rats to reduce the ohmic component of airway resistance, decreasing the ohmic inspiratory WOB. The elastic and viscoelastic components are unaltered. Hysteresis is also unaltered, suggesting that NO has negligible effects on alveolar surfactant activity.

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“…In the developing lung, NO participates in pulmonary vascularization, alveolarization, and airway branching, and also counteracts apoptosis in multiple lung cell types (3)(4)(5)(6). In the perinatal period, epithelium-derived NO is critically involved in the regulation of lung liquid production and of peripheral contractile elements (7,8), and it also mediates pulmonary vasomotor tone (9). In studies of lungs from fetal baboons, we showed that all three NOS isoforms, neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS), are principally expressed in proximal respiratory epithelium, and that there are maturational increases in their abundance and in NO production during the early third trimester (10).…”

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confidence: 99%

Postnatal Estradiol Up-regulates Lung Nitric Oxide Synthases and Improves Lung Function in Bronchopulmonary Dysplasia

McCurnin

Pierce

Willis³

et al. 2009

Am J Respir Crit Care Med

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Rationale: Nitric oxide (NO) plays an important role in lung development and perinatal lung function, and pulmonary NO synthases (NOS) are decreased in bronchopulmonary dysplasia (BPD) following preterm birth. Fetal estradiol levels increase during late gestation and estradiol up-regulates NOS, suggesting that after preterm birth estradiol deprivation causes attenuated lung NOS resulting in impaired pulmonary function. Objective: To test the effects of postnatal estradiol administration in a primate model of BPD over 14 days after delivery at 125 days of gestation (term 5 185 d). Methods: Cardiopulmonary function was assessed by echocardiography and whole body plethysmography. Lung morphometric and histopathologic analyses were performed, and NOS enzymatic activity and abundance were measured. Measurements and Main Results: Estradiol caused an increase in blood pressure and ductus arteriosus closure. Expiratory resistance and lung compliance were also improved, and this occurred before spontaneous ductal closure. Furthermore, both oxygenation and ventilation indices were improved with estradiol, and the changes in lung function and ventilatory support requirements persisted throughout the study period. Whereas estradiol had negligible effect on indicators of lung inflammation and on lung structure assessed after the initial 14 days of ventilatory support, it caused an increase in lung neuronal and endothelial NOS enzymatic activity. Conclusions: In a primate model of BPD, postnatal estradiol treatment had favorable cardiovascular impact, enhanced pulmonary function, and lowered requirements for ventilatory support in association with an up-regulation of lung NOS. Estradiol may be an efficacious postnatal therapy to improve lung function and outcome in preterm infants.The signaling molecule nitric oxide (NO), generated by nitric oxide synthase (NOS), plays a key role in multiple processes in the mature lung (1, 2). In the developing lung, NO participates in pulmonary vascularization, alveolarization, and airway branching, and also counteracts apoptosis in multiple lung cell types (3-6). In the perinatal period, epithelium-derived NO is critically involved in the regulation of lung liquid production and of peripheral contractile elements (7, 8), and it also mediates pulmonary vasomotor tone (9). In studies of lungs from fetal baboons, we showed that all three NOS isoforms, neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS), are principally expressed in proximal respiratory epithelium, and that there are maturational increases in their abundance and in NO production during the early third trimester (10). Thus, pulmonary NOS expression is up-regulated during fetal development in the primate, and this process may be critical to lung structural development and airway, parenchymal, and pulmonary vascular function in the early postnatal period.Bronchopulmonary dysplasia (BPD) is a devastating primary complication of premature birth that develops in the preterm human lung following ventilatory and oxyg...

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Endogenous nitric oxide modulates responses of tissue and airway resistance to vagal stimulation in piglets

Cited by 18 publications

References 36 publications

Surfactant Composition and Function in a Primate Model of Infant Chronic Lung Disease: Effects of Inhaled Nitric Oxide

Surfactant Composition and Function in a Primate Model of Infant Chronic Lung Disease: Effects of Inhaled Nitric Oxide

The Effect of N<sup>G</sup>-Nitro-<i>L</i>-Arginine Methyl Ester, a Nitric Oxide Synthase Inhibitor, on Respiratory Mechanics in Rats

Postnatal Estradiol Up-regulates Lung Nitric Oxide Synthases and Improves Lung Function in Bronchopulmonary Dysplasia

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