Expressions of adrenomedullin mRNA and protein in rats with hypobaric hypoxia-induced pulmonary hypertension

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 55; no. 6; pp. 2159 - 2168
• Main Authors: NAKANISHI, Kuniaki, OSADA, Hiroshi, UENOYAMA, Maki, KANAZAWA, Fumiko, OHRUI, Nobuhiro, MASAKI, Yoshinori, HAYASHI, Takuya, KANATANI, Yasuhiro, IKEDA, Tomosumi, KAWAI, Toshiaki
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Physiological Society 01.06.2004
• Subjects: Biological and medical sciences; Gene expression; Hypertension; Medical sciences; Pneumology; Proteins; Pulmonary arteries; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Ribonucleic acid; RNA; Rodents; Immunohistochemistry; Molecular hybridization; Animal model; Rat; Adrenomedullin; Cardiovascular disease; Environmental factor; Messenger RNA; RT-PCR; Hypobarism; Oxygen; Respiratory disease; Rodentia; Gene expression; Pulmonary hypertension; Polymerase chain reaction; Vertebrata; Experimental disease; Mammalia; Animal; Hypoxia; cardiac hypertrophy; cardiovascular hormone; Hypertrophy; in situ hybridization
• ISSN: 0363-6135; 1522-1539

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. [PUBLICATION ABSTRACT]