Expression of endothelin-1 in the brain and lung of rats exposed to permanent hypobaric hypoxia

Fumiko Kanazawa, Kuniaki Nakanishi, Hiroshi Osada, Yoshiki Kanamaru, Nobuhiro Ohrui, Maki Uenoyama, Yoshinori Masaki, Yasuhiro Kanatani, Sadayuki Hiroi, Susumu Tominaga, Ayako Yakata-Suzuki, Shigeo Matsuyama, Toshiaki Kawai

研究成果: Contribution to journalArticle査読

19 被引用数 (Scopus)


High-altitude hypoxia causes pulmonary hypertension in humans and animals. Endothelin-1 (ET-1) is a novel and long-lasting vasoconstrictor. However, no study has dealt with the effects of a hypobaric hypoxic environment (HHE) on ET-1 activity in the brain. We examined 134 male rats permanently exposed to the equivalent of 5500 m altitude for 1 to 8 weeks. In these HHE rats, the mean pulmonary arterial pressure was significantly raised. The level of ET-1 protein, measured by enzyme immunoassay, increased rapidly in the lungs on exposure to HHE, but decreased in the brain. The level of ET-1 mRNA, measured by semiquantitative RT-PCR, was raised at 1, 4, and 6 weeks' exposure in the lungs and at 4 or more weeks' exposure in 3 of 8 brain regions. By in situ hybridization and immunohistochemistry of brain sections, ET-1 mRNA and protein were detected in the endothelial cells, neurons, and astrocyte-like cells in control rats. In HHE rats, the immunoreactive intensity for ET-1 protein decreased rapidly with time in these cells within the brain, although a few weakly ET-1 protein-positive cells were detected until 8 weeks' exposure to HHE. Only a few weakly ET-1 mRNA-positive endothelial cells were detected in any HHE rats. Although the reactivity for ET-1 mRNA had decreased significantly in neurons and astrocyte-like cells at 1 and 2 weeks' exposure to HHE, it was again strong in both types of cells at 4 weeks' exposure to HHE. These results raise the possibility that during exposure to HHE, ET-1 production in the lung may play a role in the development of pulmonary hypertension, while a decrease in ET-1 production within the brain may help to protect neurons by preventing or limiting the constriction of cerebral microvessels during the hypoxia induced by HHE.

ジャーナルBrain Research
出版ステータス出版済み - 3 2 2005

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)
  • 分子生物学
  • 臨床神経学
  • 発生生物学


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