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Am J Physiol Heart Circ Physiol 286: H2159-H2168, 2004. First published January 8, 2004; doi:10.1152/ajpheart.00846.2003
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Expressions of adrenomedullin mRNA and protein in rats with hypobaric hypoxia-induced pulmonary hypertension

Kuniaki Nakanishi,1,2,3 Hiroshi Osada,2 Maki Uenoyama,1 Fumiko Kanazawa,2 Nobuhiro Ohrui,2 Yoshinori Masaki,1 Takuya Hayashi,1 Yasuhiro Kanatani,1 Tomosumi Ikeda,1 and Toshiaki Kawai3

1Division of Environmental Medicine, National Defense Medical College Research Institute, Tokorozawa 359-8513; 2Biochemical Section, Second Division, Aeromedical Laboratory, Japan Air Self-Defense Force, Tachikawa 190-0003; and 3Department of Pathology, National Defense Medical College, Tokorozawa 359-8513, Japan

Submitted 8 September 2003 ; accepted in final form 29 December 2003

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.

cardiovascular hormone; cardiac hypertrophy; RT-PCR; immunohistochemistry; in situ hybridization



Address for reprint requests and other correspondence: K. Nakanishi, Dept. of Pathology, National Defense Medical College, Tokorozawa 359-8513, Japan (E-mail: nknsknak{at}res.ndmc.ac.jp).




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