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

• Published in: Brain research Vol. 1036; no. 1; pp. 145 - 154
• Main Authors: Kanazawa, Fumiko, Nakanishi, Kuniaki, Osada, Hiroshi, Kanamaru, Yoshiki, Ohrui, Nobuhiro, Uenoyama, Maki, Masaki, Yoshinori, Kanatani, Yasuhiro, Hiroi, Sadayuki, Tominaga, Susumu, Yakata-Suzuki, Ayako, Matsuyama, Shigeo, Kawai, Toshiaki
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 02.03.2005; Amsterdam Elsevier; New York, NY
• Subjects: Altitude Sickness - complications; Altitude Sickness - metabolism; Altitude Sickness - physiopathology; Animals; Astrocyte; Astrocytes - metabolism; Biochemistry and metabolism; Biological and medical sciences; Brain; Brain - metabolism; Brain - physiopathology; Central nervous system; Cerebrovascular Circulation - physiology; Disease Models, Animal; Down-Regulation - physiology; Endothelial Cells - metabolism; Endothelin-1; Endothelin-1 - genetics; Endothelin-1 - metabolism; Fundamental and applied biological sciences. Psychology; Hypertension, Pulmonary - etiology; Hypertension, Pulmonary - metabolism; Hypertension, Pulmonary - physiopathology; Hypobaric hypoxia; Hypoxia - complications; Hypoxia - metabolism; Hypoxia - physiopathology; Hypoxia, Brain - etiology; Hypoxia, Brain - metabolism; Hypoxia, Brain - physiopathology; Immunohistochemistry; Lung - metabolism; Lung - physiopathology; Male; Neurons - metabolism; Rats; Rats, Wistar; Regional Blood Flow - physiology; RNA, Messenger - metabolism; Time Factors; Up-Regulation - physiology; Vasoconstriction - physiology; Vertebrates: nervous system and sense organs; Hypobaric hypoxia; Endocrine and autonomic regulation; Brain; Astrocyte; Endothelin-1; Oxygen; Rat; Neuroglia; Lung; Rodentia; Central nervous system; Endothelin 1; Respiratory system; Encephalon; Hypobaric hypoxia; Endothelin-1; Vertebrata; Mammalia; Animal; Brain; Astrocyte; Hypoxia; Arterial pressure; Hemodynamics; Hypobarism
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2004.12.019

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.