American journal of physiology. Lung cellular and molecular physiology
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Am. J. Physiol. Lung Cell Mol. Physiol. · Mar 2005
In vivo inosine protects alveolar epithelial type 2 cells against hyperoxia-induced DNA damage through MAP kinase signaling.
Inosine, a naturally occurring purine with anti-inflammatory properties, was assessed as a possible modulator of hyperoxic damage to the pulmonary alveolar epithelium. Rats were treated with inosine, 200 mg/kg ip, twice daily during 48-h exposure to >90% oxygen. The alveolar epithelial type 2 cells (AEC2) were then isolated and cultured. ⋯ ERK1/2 was activated both in freshly isolated and 24-h-cultured AEC2 by in vivo inosine treatment, whereas blockade of the MAPK pathway in vitro reduced the protective effect of in the vivo inosine treatment. Together, the data suggest that inosine treatment during hyperoxic exposure results in protective signaling mediated through pathways downstream of MEK. Thus inosine may deserve further evaluation for its potential to reduce hyperoxic damage to the pulmonary alveolar epithelium.
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Am. J. Physiol. Lung Cell Mol. Physiol. · Mar 2005
ReviewDistensibility of the normal human lung circulation during exercise.
Increasing pulmonary arterial (Ppa) and wedge (Pw) pressures at high flow (Q) during exercise could distend the thin-walled vessels. A mechanical descriptor of vascular distension, the distensibility (alpha, fractional diameter change/mmHg pressure), has been reported to be approximately 0.02 for isolated large and small arteries, i.e., a 2% change in diameter per millimeter mercury pressure. In this review we used a pulmonary hemodynamic model to estimate alpha for data from exercising humans to determine whether interpretable results might be obtained. ⋯ Values of alpha tended to decrease with age in men >60 yr. Thus at rest and during exercise, normal values of alpha in young persons were similar to those measured in vitro, and the values decreased in chronic hypoxia and with aging where vascular remodeling or vascular wall stiffening was expected. We propose that the estimation of pulmonary vascular distensibility in humans may be a useful descriptor of pulmonary hemodynamics.