Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodeling of the heart and pulmonary arteries. Adrenomedullin (AM) has diuretic, natriuretic, and hypotensive effects. To study the possible effects of HHE on the AM synthesis system, 150 male Wistar rats were housed in a chamber at the equivalent of a 5,500-m altitude level for 21 days. After 14 days of exposure to HHE, pulmonary arterial pressure (PAP) was significantly increased (compared with control rats). The plasma AM protein level was significantly increased on day 21 of exposure to HHE. In the right ventricle (RV), right atrium, and left atrium of the heart, the expressions of AM mRNA and protein were increased in the middle to late phase (5-21 days) of HHE, whereas in the brain and lung they were increased much earlier (0.5-5 days). In situ hybridization and immunohistochemistry showed AM mRNA and protein staining to be more intense in the RV in animals in the middle to late phase of HHE exposure than in the controls. During HHE, these changes in AM synthesis, which occurred strongly in the RV, occurred alongside the increase in PAP. Conceivably, AM may play a role in modulating pulmonary hypertension in HHE.
The present study suggests that fluvastatin attenuates HIF-1-dependent ET-1 gene expression in conjunction with the stimulation of HIF-1α ubiquitin/proteasome-dependent degradation via isoprenoid-dependent mechanisms.
Included in the Cooperative Cope Thunder exercises from Japan to Alaska is one of the longest distance flight missions carried out by Japan Air-Self Defense Force F-15 pilots. The magnitude of the flight stress of these pilots is considered to be quite high. The purpose of this study was to evaluate the flight stress induced by the long-distance flights. The subjects were eight pilots who participated on a volunteer basis. Samples of urine were collected approximately 30 minutes before (preflight) and 20 minutes after (postflight) the flights. The ratios (post-:preflight) of noradrenaline levels were 1.20 +/- 0.09 (Japan-Alaska) and 1.32 +/- 0.12 (Alaska-Japan), and those of adrenaline were 4.03 +/- 1.06 and 3.68 +/- 0.98. These results strongly suggest that psychological stress during the long-distance flights is increased in the fighter pilots.
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