Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.

T. Evaluation of cigarette smokeinduced emphysema in mice using quantitative micro-computed tomography. Am J Physiol Lung Cell Mol Physiol 308: L1039-L1045, 2015. First published March 27, 2015 doi:10.1152/ajplung.00366.2014.-Chronic cigarette smoke (CS) exposure provokes variable changes in the lungs, and emphysema is an important feature of chronic obstructive pulmonary disease. The usefulness of micro-computed tomography (CT) to assess emphysema in different mouse models has been investigated, but few studies evaluated the dynamic structural changes in a CS-induced emphysema mouse model. A novel micro-CT technique with respiratory and cardiac gating has resulted in high-quality images that enable processing for further quantitative and qualitative analyses. Adult female C57BL/6J mice were repeatedly exposed to mainstream CS, and micro-CT scans were performed at 0, 4, 12, and 20 wk. Emphysema was also histologically quantified at each time point. Air-exposed mice and mice treated with intratracheal elastase served as controls and comparisons, respectively. End-expiratory lung volume, corresponding to functional residual volume, was defined as the calculated volume at the phase of end-expiration, and it evaluated air trapping. The end-expiratory lung volumes of CS-exposed mice were significantly larger than those of air controls at 12 and 20 wk, which was in line with alveolar enlargement and destruction by histological quantification. However, CS exposure neither increased low attenuation volume nor decreased the average lung CT value at any time point, unlike the elastase-instilled emphysema model. CSexposed mice had rather higher average lung CT values at 4 and 12 wk. This is the first study characterizing a CS-induced emphysema model on micro-CT over time in mice. Moreover, these findings extend our understanding of the distinct pathophysiology of CSinduced emphysema in mice. chronic obstructive pulmonary disease; mouse THE DEFINING FEATURE OF CHRONIC obstructive pulmonary disease (COPD) is irreversible airflow obstruction caused by elevated resistance in the small airways and increased lung compliance due to emphysema and lung destruction (12). Emphysema is defined pathologically as the permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls, without obvious fibrosis (5). The severity of emphysema is clinically evaluated as low attenuation area (LAA) volume divided by total lung volume (%LAA) on high-resolution computed tomography (CT) (17). It has been reported that high %LAA of lung is related to high mortality, frequent exacerbations, and poor quality of life among COPD patients (11).Although no current animal model recapitulates all features of human COPD (26), different mouse models of emphysema are available, including intratracheal instillation of elastase, cigarette smoke (CS) exposure, and genetic alteration (24). The elastase-induced pulmonary emphysema model is known to induce severe dose-dependent alveolar destruction with rapid onse...

Five clusters of comorbidities were identified in Japanese COPD patients. The clinical characteristics and health-related quality of life were different among these clusters during a follow-up of two years.

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