[Reduced cardiopulmonary exercise capacity in patients with essential hypertension: impact of left ventricular hypertrophy].

OBJECTIVE: To evaluate the cardiopulmonary exercise capacity in patients with essential hypertension (EH) complicating with or without left ventricular hypertrophy (LVH). METHODS: Graded maximal exercise test on the bicycle ergometer with respiratory gas analysis were performed in 30 gender and age matched normotensive controls, 40 EH patients without LVH and 30 EH patients with LVH (LVMI>125 g/m2 in males and > 120 g/m2 in females). Metabolic equivalents (METs), oxygen uptake (VO2), oxygen uptake to body mass ratio (VO2/kg) and oxygen uptake to heart beat ratio (VO2/HR) at time of reaching anaerobic threshold (AT) and at maximal oxygen uptake (VO2max) were measured and compared. RESULTS: METs and VO2/kg were significantly reduced in EH patients with or without LVH compared with controls [at AT, METs: 3.57 +/- 0.8 and 4.34 +/- 1.47 vs. 5.21 +/- 1.45; VO2/kg: 12.38 +/- 2.85 and 14.42 +/- 4.33 vs. 18.48 +/- 4.52, all P < 0.01; at VO2max, METs: 4.94 +/- 1.24 and 5.90 +/- 1.51 vs. 6.96 +/- 1.85; VO(2)/kg: (17.20 +/- 4.34) mlxmin(-1)xkg(-1) and (20.41 +/- 4.59) mlxmin(-1)xkg(-1) vs. (24.04 +/- 5.21) mlxmin(-1)xkg(-1), all P < 0.01]. METs and VO2/kg at both time points were also significantly reduced in EH patients with LVH compared EH patients without LVH (all P < 0.05). The lower VO2/kg in hypertensive patients was significantly correlated to higher LVMI (P < 0.05). CONCLUSIONS: Cardiopulmonary exercise capacity was reduced in hypertensive patients, especially in hypertensive patients with LVH.

Multiple pulmonary adenomas in the lung of transgenic mice overexpressing the RON receptor tyrosine kinase. Recepteur d'origine nantais.

The receptor tyrosine kinase RON (recepteur d'origine nantais), a member of the MET proto-oncogene family, has been implicated in the pathogenesis of certain epithelial cancers including lung adenocarcinomas. To determine the oncogenic potential of RON, transgenic mice were generated using the surfactant protein C promoter to express human wild-type RON in the distal lung epithelial cells. The mice were born normal without morphological defects in the lung, however, multiple lung adenomas with distinct morphology and growth pattern were observed. Tumors appeared as a single mass in the lung around 2 months of age and gradually developed into multiple nodules throughout the lung. Most of the tumors were characterized as cuboidal epithelial cells with type II cell phenotypes. They grew along the alveolar walls and projected into the alveolar septa. A transition from pre-malignant adenomas to adenocarcinomas was observed. The RON transgene is highly expressed and constitutively activated in the tumors as evident by immunohistochemical staining and western blot analyses. Moreover, we found that Ras expression was dramatically increased in the majority of tumors. However, no mutation in the 'hot spots' of the K-Ras or p53 gene was observed, although limited genomic instability occurs in individual tumors. Taken together, this is a mouse lung tumor model with unique biological characteristics. The model may provide an opportunity to study the role of RON in lung tumors and to elucidate the mechanisms underlying this distinct lung tumor.