Osteopontin expression in normal and hypobaric hypoxia-exposed rats.
OBJECTIVE
Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodelling of the heart and pulmonary arteries. Osteopontin (OPN) has emerged as a key factor in cardiovascular remodelling in response to pressure or volume overload. We studied the possible effects of HHE on the OPN synthesis system.


METHODS
One hundred and forty-eight male Wistar rats were housed in a chamber with conditions equivalent of an altitude of 5500 m for up to 21 days.


RESULTS
Plasma OPN protein level was found to be significantly decreased on day 0.5 of exposure to HHE, as was the level in the adrenal gland (which secreted highest levels of OPN protein). In the right ventricle of the heart (mRNA) and the lung (protein), OPN expression was found to be significantly increased only on day 1 and day 5, respectively, of exposure to HHE. By immunohistochemistry, the distribution and intensity of OPN protein in several organs were found to alter during exposure to HHE. However, these changes in OPN synthesis did not coincide with the moderate increase in pulmonary arterial pressure (PAP) (maximal mean PAP, 24.5 mmHg) during HHE.


CONCLUSIONS
Pulmonary hypertension in HHE with conditions equivalent of an altitude of 5500 m may induce little or no OPN in heart and lung. Sustained induction may require a more severe PAP overload.
Uenoyama
M
M
Division of Environmental Medicine, National Defense Medical College Research Institute, Tokorozawa, Japan.
Ogata
S
S
Nakanishi
K
K
Kanazawa
F
F
Hiroi
S
S
Tominaga
S
S
Kanatani
Y
Y
Seo
A
A
Matsui
T
T
Suzuki
S
S
D000531:Altitude; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001794:Blood Pressure; D001835:Body Weight; D015870:Gene Expression; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D053495:Osteopontin / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D011651:Pulmonary Artery / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D012333:RNA, Messenger; D053495:Osteopontin