Decreased pulmonary vascular resistance during nasal breathing: modulation by endogenous nitric oxide from the paranasal sinuses

Settergren, G.; Angdin, Monika; Astudillo, Rafael; Gelinder, S.; Líška, Ján; Lundberg, Jon O.; Weitzberg, Eddie

doi:10.1046/j.1365-201x.1998.00352.x

Cited by 44 publications

(27 citation statements)

References 14 publications

(15 reference statements)

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“…Consistent with this hypothesis, impaired pulmonary NO synthesis in iNOS-/-mice is associated with augmented hypoxia-induced pulmonary hypertension [20], and aerosol-mediated iNOS gene transfer in the bronchial tree of rats attenuates hypoxic pulmonary hypertension [21]. In humans, pulmonary artery pressure is lower during nasal than during oral breathing [22], and impaired lower respiratory tract NO production is associated with exaggerated hypoxic pulmonary vasoconstriction [23]. Taken together, these data are consistent with the concept that NO derived from the respiratory tract participates in the regulation of pulmonary artery pressure.…”

Section: Discussionsupporting

confidence: 61%

Increased eNO and pulmonary iNOS expression in eNOS null mice

Cook¹,

Vollenweider²,

Ménard³

et al. 2003

Eur Respir J

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Increased eNO and pulmonary iNOS expression in eNOS null mice. S. Cook, P. Vollenweider, B. Ménard, M. Egli, P. Nicod, U. Scherrer. #ERS Journals Ltd 2003. ABSTRACT: Nitric oxide (NO) is a major regulatory molecule of the cardiovascular system; however, measurement of vascular NO synthesis in vivo represents a major challenge. NO stemming from the lower respiratory tract has been used as a marker of vascular endothelial function. Experimental evidence for this concept is lacking. Therefore, the aim of the present study was to investigate this relationship.Lower respiratory tract exhaled NO concentration, together with systemic and pulmonary artery pressure, was measured in endothelial nitric oxide synthase (NOS) (eNOS) null mice (eNOS-/-). Similar studies were performed in inducible NOS (iNOS) null mice (iNOS-/-).Defective endothelial NO synthesis in eNOS-/-mice (evidenced by systemic and pulmonary hypertension) was associated with augmented exhaled NO levels (12.5¡1.9 versus 9.8¡1.2 parts per billion (ppb), eNOS-/-versus wild type), whereas normal endothelial NO synthesis in iNOS-/-mice was associated with decreased exhaled NO levels (4.3 ¡ 1.5 ppb). Augmented exhaled NO levels in eNOS-/-mice were associated with upregulation of iNOS expression in the lung.These results indicate that inducible nitric oxide synthase is a major determinant of gaseous nitric oxide production in the lung, and lower respiratory tract exhaled nitric oxide does not always represent a marker of vascular endothelial nitric oxide synthesis. Since the late 1980s, nitric oxide (NO) has emerged as a major regulator of the cardiovascular system [1]. Measurement of vascular endothelial nitric oxide synthase (NOS) (eNOS) activity and its final product NO in vivo still represents a major challenge, because the small amount of NO produced by the endothelium is rapidly scavenged by haemoglobin and then inactivated. To date, the contribution of NO to the regulation of vascular tone has been assessed by indirect methods, examining specific modifications of physiological responses induced by NOS inhibitors and NO donors, and/or measuring levels of NO metabolites or cyclic guanosine monophosphate [2].NO is present in the exhaled air of many animal species and humans [3], but its origin and physiological function are incompletely understood. In the respiratory tract, all three NOS isoforms are expressed in tissues close to the airways. Although there is consensus that under normal conditions, a large proportion of the exhaled NO is synthesised by inducible NOS (iNOS) located in the epithelial cells of the upper respiratory tract [4,5], the origin and function of lower respiratory tract exhaled NO is incompletely understood. It has been claimed that exhaled NO stemming from the lower respiratory tract represents a marker of vascular endothelial NO synthesis [6][7][8][9][10][11][12]. Experimental evidence for this concept is lacking, however, and studies in humans, using pharmacological NOS inhibitors, suggest that eNOS barely albeit significantly, cont...

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Section: Discussionsupporting

confidence: 61%

Increased eNO and pulmonary iNOS expression in eNOS null mice

Cook¹,

Vollenweider²,

Ménard³

et al. 2003

Eur Respir J

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“…There is evidence in humans, that in addition to pulmonary endothelial, respiratory epithelial NO also regulates pulmonary artery pressure [ 18 ]. In line with this hypothesis, we and others found that alveolar epithelial NO synthesis (as evidenced by lower respiratory tract exhaled NO) is defective in HAPE-prone subjects [ 19 , 20 ].…”

Section: Short-term Cardiovascular Adaptation To Hypoxiasupporting

confidence: 61%

Novel Insights into Cardiovascular Regulation in Patients with Chronic Mountain Sickness

Rimoldi

Rexhaj

Villena

et al. 2016

Advances in Experimental Medicine and Biology

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Studies of high-altitude populations, and in particular of maladapted subgroups, may provide important insight into underlying mechanisms involved in the pathogenesis of hypoxemia-related disease in general. Chronic mountain sickness (CMS) is a major public health problem in mountainous regions of the world affecting many millions of high-altitude dwellers. It is characterized by exaggerated chronic hypoxemia, erythrocytosis, and mild pulmonary hypertension. In later stages these patients often present with right heart failure and are predisposed to systemic cardiovascular disease, but the underlying mechanisms are poorly understood. Here, we present recent new data providing insight into underlying mechanisms that may cause these complications.

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“…Two recent studies found a trend towards better gas exchange with partial elimination or diversion of endogenous NO production. SETTERGREN et al [42] eliminated the autoinhalation of nasal and sinus NO in humans and FAGAN et al [43] abolished endothelial cell production of NO in a knockout mouse deficient in endothelial NOS. These findings strongly suggest the intriguing possibility that endogenous basal NO production in the lung or upper respiratory tract does not serve the purpose of regulating V '/Q '.…”

Section: Differences Between Effects Of Nmentioning

confidence: 99%

Pulmonary NO synthase inhibition and inspired CO2: effects on V ′/Q ′ and pulmonary blood flow distribution

Brogan¹,

Hedges²,

McKinney³

et al. 2000

Eur Respir J

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Inhaled carbon dioxide decreases ventilation/perfusion ratio (V '/Q ') heterogeneity in dogs. The aim of this study was to test whether inhaled CO 2 improves the V '/Q ' by inhibition of nitric oxide production and whether inhibition of endogenous NO production in the lung alters gas exchange and V '/Q ' matching.Eleven healthy dogs were anaesthetized and mechanically ventilated. The multiple inert gas elimination technique (MIGET) was used to measure V '/Q ' heterogeneity and regional pulmonary blood flow heterogeneity was assessed in five dogs using fluorescent microspheres. In a separate set of five dogs, exhaled NO levels were measured via chemiluminescence. All dogs were studied before and after 4.8% inspired CO 2 , and then given the NO synthase inhibitor N v -nitro-L-arginine methyl ester (L-NAME, 10 mg . kg -1 ) via nebulization, after which they were studied again with room air and inhaled CO 2 .CO 2 and L-NAME improved arterial and alveolar oxygen tension, but the improvements with L-NAME did not reach statistical significance. Improved V '/Q ' matching, as assessed by the MIGET, occurred under all experimental conditions. Exhaled NO levels were reduced by 40% with CO 2 and 70% with L-NAME. The standard deviation of regional pulmonary blood flow assessed via microspheres decreased only with inhaled CO 2 . Fractal analysis of pulmonary blood flow distributions revealed that regional blood flow was highly correlated with flow to neighbouring pieces of lung in all four conditions with no changes in the fractal dimension.Inspired carbon dioxide improves ventilation perfusion ratio matching and is associated with a more homogeneous distribution of pulmonary blood flow. Although inspired carbon dioxide causes a reduction in exhaled nitric oxide, the differences in pulmonary perfusion distributions found between carbon dioxide and N v -nitro-Larginine methyl ester suggest that the carbon dioxide effect is not mediated by a reduction in nitric oxide production. The improved ventilation perfusion ratio matching with inhibition of nitric oxide synthase suggests the intriguing possibility requiring further study that endogenous production of nitric oxide in the lung does not subserve ventilation perfusion ratio regulation. Eur Respir J 2000; 16: 288±295. Addition of low concentrations (2±5%) of carbon dioxide to inspired gas improves gas exchange and arterial oxygenation in normal lungs [1,2]. Using the multiple inert gas elimination technique (MIGET), it was demonstrated that inspired CO 2 reduces ventilation/perfusion ratio (V '/Q ') heterogeneity even with constant ventilation [3]. Although CO 2 has many effects on the lungs that may promote V '/Q ' matching [4,5], it remains unknown how and at what site(s) CO 2 decreases V '/Q ' heterogeneity.Changes in CO 2 concentration or the accompanying pH may affect airways, parenchyma or vessels directly or indirectly through modulation of effector substances such as prostaglandins [6] or calcium [7]. Of considerable interest, also, is nitric oxide, which is ...

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Decreased pulmonary vascular resistance during nasal breathing: modulation by endogenous nitric oxide from the paranasal sinuses

Cited by 44 publications

References 14 publications

Increased eNO and pulmonary iNOS expression in eNOS null mice

Increased eNO and pulmonary iNOS expression in eNOS null mice

Novel Insights into Cardiovascular Regulation in Patients with Chronic Mountain Sickness

Pulmonary NO synthase inhibition and inspired CO2: effects on V ′/Q ′ and pulmonary blood flow distribution

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