Hypoxic pulmonary vasoconstriction

Dumas, Jean-Paul; Bardou, Marc; Goirand, Françoise; Dumas, Monique

doi:10.1016/s0306-3623(99)00026-9

Cited by 73 publications

(48 citation statements)

References 87 publications

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“…One of the possible implications in clinical practice would be the pharmacological decrease in peripheral pulmonary vascular resistance during hypoxia, in agreement with recent studies showing bene®cial effects of calcium channel blockers during high altitude pulmonary oedema [29]. This model could help to select new drugs such as other potassium channel openers or endothelin receptor antagonists that could be useful in clinical practice [30].…”

Section: Levcromakalimsupporting

confidence: 71%

Role of NO pathway, calcium and potassium channels in the peripheral pulmonary vascular tone in dogs

Chabot

Schrijen²,

Saunier³

2001

Eur Respir J

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Because hypoxic pulmonary vasoconstriction occurs mainly in the small pulmonary arteries, the authors investigated the effects of drugs acting on the nitric oxide (NO) pathway and the calcium and potassium channels in the peripheral pulmonary circulation, without interference with the overall pulmonary or systemic circulation.Mixed venous blood was infused in wedged areas to study the pressure/¯ow relationship and to compute peripheral pulmonary vascular resistance (PPVR). The authors studied the effects of N v -nitro-l-arginine methyl ester (l-NAME), an NO synthase inhibitor, sodium nitroprusside (SNP, an NO donor), the calcium channel blockers verapamil, nifedipine and nicardipine, and the potassium channel opener levcromakalim, during normoxia and acute mild normocapnic hypoxia.In the peripheral pulmonary circulation, l-NAME caused an increase in PPVR during normoxia (z95%; p<0.001) and hypoxia (z60%; p<0.01). Following the increase by l-NAME, SNP decreased PPVR during normoxia (-24%; p<0.05) and hypoxia (-23%; p<0.05). Verapamil, nifedipine and nicardipine did not modify PPVR during normoxia but during hypoxia they decreased PPVR (-28%, nonsigni®cant; -27%, p<0.01 and -33%, p<0.05, respectively). Levcromakalim did not modify PPVR during normoxia or hypoxia.In conclusion, the nitric oxide pathway and voltage-dependent calcium channels, and not adenosine triphosphate sensitive potassium channels, play an important role in the control of peripheral pulmonary circulation in dogs. Segmental differences in vasomotor reactivity are well documented in the pulmonary vasculature. Hypoxia causes sustained constriction in resistance pulmonary arteries [1] while causing a biphasic response in conduit pulmonary arteries [2]. Investigations on resistance vessels have been performed mainly in vitro on small isolated pulmonary artery rings. Some authors investigated the relationship between pressure and¯ow in the pulmonary circulation in vivo for a lobe in situ [3], but the preparation included predominantly conduit vessels and the¯ow changes induced modi®cations of other variables. Because alveolar hypoxia is an important regulator of pulmonary vascular tone and causes vasoconstriction mainly in small pulmonary arteries, the authors studied, in vivo, the pharmacology of the vasomotor response of the peripheral pulmonary circulation, during normoxia and mild acute hypoxia.Under physiological conditions, the vasodilator nitric oxide (NO) is continually released by endothelial cells and regulates organ and perfusion pressure and¯ow [4]. Endogenous NO may contribute to the maintenance of normal pulmonary vasomotor tone. Pulmonary vascular tone is also regulated by the activity of calcium and potassium channels, and the links between activation of both calcium and potassium channels and NO-induced relaxation in the proximal part of the pulmonary artery have been emphasized, in vitro [5]. Various inhibitors of NO synthase (NOS) have been shown to increase the normoxic pulmonary vascular tone in some [6,7] but not in all...

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Section: Levcromakalimsupporting

confidence: 71%

Role of NO pathway, calcium and potassium channels in the peripheral pulmonary vascular tone in dogs

Chabot

Schrijen²,

Saunier³

2001

Eur Respir J

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“…Likewise, ventilated areas with abnormal surfactant may be underperfused with resultant arterial hypoxemia. Severe hypoxia induces pulmonary vasoconstriction mediated by pulmonary arterial vascular small muscle contraction (35)(36)(37). Hypoxia induced vasoconstriction when oxygen saturation is under 50% in all species so far examined (36,38,39).…”

Section: Discussionmentioning

confidence: 99%

“…Severe hypoxia induces pulmonary vasoconstriction mediated by pulmonary arterial vascular small muscle contraction (35)(36)(37). Hypoxia induced vasoconstriction when oxygen saturation is under 50% in all species so far examined (36,38,39). The decreased alveolar capillary size presently observed in SP-B-deleted mice is distinct from that caused by hypoxic vasoconstriction.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Surfactant Surface Tension Influences Alveolar Capillary Shape and Oxygenation

Ikegami

Weaver

Grant

et al. 2009

Am J Respir Cell Mol Biol

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Alveolar capillaries are located in close proximity to the alveolar epithelium and beneath the surfactant film. We hypothesized that the shape of alveolar capillaries and accompanying oxygenation are influenced by surfactant surface tension in the alveolus. To prove our hypothesis, surfactant surface tension was regulated by conditional expression of surfactant protein (SP)-B in Sftpb 2/2 mice, thereby inhibiting surface tension-lowering properties of surfactant in vivo within 24 hours after depletion of Sftpb. Minimum surface tension of isolated surfactant was increased and oxygen saturation was significantly reduced after 2 days of SP-B deficiency in association with deformation of alveolar capillaries. Intravascularly injected 3.2-mmdiameter microbeads through jugular vein were retained within narrowed pulmonary capillaries after reduction of SP-B. Ultrastructure studies demonstrated that the capillary protrusion typical of the normal alveolar-capillary unit was reduced in size, consistent with altered pulmonary blood flow. Pulmonary hypertension and intrapulmonary shunting are commonly associated with surfactant deficiency and dysfunction in neonates and adults with respiratory distress syndromes. Increased surfactant surface tension caused by reduction in SP-B induced narrowing of alveolar capillaries and oxygen desaturation, demonstrating an important role of surface tension-lowering properties of surfactant in the regulation of pulmonary vascular perfusion.Keywords: surfactant protein-B; transgenic mice; pulmonary blood flow; acute respiratory distress syndrome; pulmonary vascular perfusion Pulmonary surfactant is a complex mixture of lipids and associated proteins that are required for formation and stability of surfactant film in the alveolus. After secretion from type II epithelial cells, surfactant forms a lipid rich film that covers the entire alveolar surface, reducing surface tension at the air/liquid interface from 70 mN/m to near 0 mN/m (1). The reduction of alveolar surface tension is required for the maintenance of alveolar surface area, upon which respiration depends. Surfactant function requires the presence of surfactant protein (SP)-B, a small hydrophobic protein that is tightly associated with surfactant phospholipids in the alveolus (1, 2). In humans and mice, SP-B deficiency or mutations in SFTPB cause respiratory failure and death in adults and neonates (3-5). Conditional reduction of SP-B for 4 days in adult mice causes respiratory failure associated with abnormal high surface tension of the surfactant present in bronchoalveolar lavage fluid (BALF) (6-8). This conditional SP-B mouse provides a useful model for study of the influence of surface tension on lung structure, function, and inflammation in adult lung in vivo. The loss of surfactant surface activity influences the shape and function of cells beneath the surfactant film. For example, reduction in SP-B increases the surface tension of surfactant, influencing both cell shape and phagocytic activity of alveolar macrophages in vivo...

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“…In terms of lung function, the characteristic alteration in patients with PAH/CTEPH is a reduction in diffusing capacity while lung volumes are generally within normal limits (69). Exposure to hypobaric hypoxia at altitude or during air flights increases PAP through hypoxic pulmonary vasoconstriction already in healthy individuals and, presumably, even more in patients with PH due to their impaired hemodynamics and gas exchange (10,34,67). According to questionnaire assessments on flight experience, the percentage of PH patients perceiving symptoms during exposure to a moderately hypoxic environment like commercial air travel (with minimal cabin pressure equivalent to 2,437 m) is mostly small (64).…”

Section: Effect Of Hypobaric Hypoxia On Exercise Performance In Patiementioning

confidence: 99%

Effect of hypoxia and hyperoxia on exercise performance in healthy individuals and in patients with pulmonary hypertension: a systematic review

Ulrich

Schneider

Bloch

2017

Journal of Applied Physiology

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Exercise performance is determined by oxygen supply to working muscles and vital organs. In healthy individuals, exercise performance is limited in the hypoxic environment at altitude, when oxygen delivery is diminished due to the reduced alveolar and arterial oxygen partial pressures. In patients with pulmonary hypertension, exercise performance is already reduced near sea level due to impairments of the pulmonary circulation and gas exchange and, presumably, these limitations are more pronounced at altitude. In studies performed near sea level in healthy subjects as well as in patients with pulmonary hypertension (PH) maximal performance during progressive ramp exercise and endurance of submaximal constant load exercise were substantially enhanced by breathing oxygen-enriched air. Both in healthy individuals and in PH-patients these improvements were mediated by a better arterial, muscular and cerebral oxygenation along with a reduced sympathetic excitation, as suggested by the reduced heart rate and alveolar ventilation at submaximal isoloads, and an improved pulmonary gas exchange efficiency, especially in patients with PH. In summary, in healthy individuals and in patients with pulmonary hypertension, alterations in the inspiratory PO2 by exposure to hypobaric hypoxia or normobaric hyperoxia reduce or enhance exercise performance, respectively, by modifying oxygen delivery to the muscles and the brain, by effects on cardiovascular and respiratory control and by alterations in pulmonary gas exchange. The understanding of these physiologic mechanisms helps counselling individuals planning altitude or air travel and prescribing oxygen therapy to patients with pulmonary hypertension. is determined by oxygen supply to working muscles and vital organs. In healthy individuals, exercise performance is limited in the hypoxic environment at altitude, when oxygen delivery is diminished due to the reduced alveolar and arterial oxygen partial pressures. In patients with pulmonary hypertension (PH), exercise performance is already reduced near sea level due to impairments of the pulmonary circulation and gas exchange, and, presumably, these limitations are more pronounced at altitude. In studies performed near sea level in healthy subjects, as well as in patients with PH, maximal performance during progressive ramp exercise and endurance of submaximal constant-load exercise were substantially enhanced by breathing oxygen-enriched air. Both in healthy individuals and in PH patients, these improvements were mediated by a better arterial, muscular, and cerebral oxygenation, along with a reduced sympathetic excitation, as suggested by the reduced heart rate and alveolar ventilation at submaximal isoloads, and an improved pulmonary gas exchange efficiency, especially in patients with PH. In summary, in healthy individuals and in patients with PH, alterations in the inspiratory PO 2 by exposure to hypobaric hypoxia or normobaric hyperoxia reduce or enhance exercise performance, respectively, by modifying oxygen deliv...

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Hypoxic pulmonary vasoconstriction

Cited by 73 publications

References 87 publications

Role of NO pathway, calcium and potassium channels in the peripheral pulmonary vascular tone in dogs

Role of NO pathway, calcium and potassium channels in the peripheral pulmonary vascular tone in dogs

Pulmonary Surfactant Surface Tension Influences Alveolar Capillary Shape and Oxygenation

Effect of hypoxia and hyperoxia on exercise performance in healthy individuals and in patients with pulmonary hypertension: a systematic review

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