plasma of PA and TA and in extractives of lung tissues of hypoxic rats were significantly
enhanced along with prolonging the time of exposure to CINH. Correlativity analysis: DMPA and
PTMA had positive correlation with the extent of HPH and the increase of adrenomedullin level
in plasma of PA and TA and in extractives of lung tissues were in proportion to the extent of
HPH. Conclusion: Hypoxia is effective in promoting ADM synthesis and release in pulmonary
tissue and suggests that ADM as vasodilator peptide plays an important regulating role on
pulmonary circulation and pulmonary vascular structural remodeling in the pathophysiological
process of HPH.
113.
EFFECTS OF CHLORAMPHENICOL ADMINISTRATION ON MITOCHONDRIAL
RESPIRATORY FUNCTION AND CYTOCHROME C OXIDASE ACTIVITY AFTER
ACUTE AND PROLONGED HYPOXIA EXPOSURE. Liu Junze
1
, Chen Lifeng
1
, Song Rong
1
.
Department of Pathophysiology, The Third Military Medical University, Chongqing, P R China
1
.
The mitochondrial dyfunction resulting from hypoxia is a key factor for the disorder in brain
energy metabolism. In order to know adaptive alteration of mitochondrial oxidative
phosphorylation during hypoxia exposure, we investigated the effects of the Chloramphenicol
(CAP) administration that inhibits mitochondrial protein synthesis on aspects of mitochondrial
oxidative respiration and cytochrome c oxidase (CytOX) activity during acute and prolonged
hypoxia exposure. Adult male Wistar rats were administrated with CAP (50mg/kg, once every 12
hours) for 7 days before sacrificed by decapitation. Acute and prolonged hypoxia were set up by
exposing rats to a hypobaric chamber simulating 5000m high altitude for 1 day and 30 days. The
cerebral cortex mitochondria were isolated and oxidative respiratory activity as well as CytOX
activity was measured by Clark oxygen electrode. The results showed that mitochondrial state 3
respiration (ST3) and respiratory control rate(RCR) and CytOX activity decreased significantly
after acute and prolonged hypoxia exposure, while state 4 respiration(ST4) increased after acute
and restore to control after prolonged hypoxia exposure. CAP administration resulted in decrease
significantly in ST3 and CytOX activity and increase in ST4 and RCR. When CAP-administered
rats exposed to hypoxia, acute exposure resulted in further decrease in ST3, but also ST4, thus
RCR further increase. While prolonged exposure of CAP-administered rats showed higher in ST3
and lower in ST4 and RCR than acute exposure. ST4 and RCR reached to control level (p0.05).
CytOX activity restored to control (p0.05) in both acute and prolonged hypoxia exposure of CAP-
administered rats. These findings suggested that the prolonged hypoxia exposure could improve
mitochondrial respiratory function. CAP administration might be beneficial to the recovery of
mitochondrial respiratory function during hypoxic exposure.
114.
THE EFFECT OF BERAPROST SODIUM ON CELL PROLIFERATION OF HUMAN
PULMONARY ARTERY SMOOTH MUSCLE CELLS. Maiko Kadowaki
1
, Shiro Mizuno
1
,
Daisuke Uesaka
1
, Yoshiki Demura
1
, Shingo Ameshima
1
, Isamu Miyamori
1
, Takeshi Ishizaki
1
.
Univercity of Fukui
1
.
Background: Hypoxia is known to cause pulmonary hypertension including pulmonary
arterial smooth muscle proliferation. It is noted that prostacyclin analogs suppress such an effect
of hypoxia and further Beraprost sodium (BPS), a stable prostacyclin analog, induces cyclin
dependent kinase (CDK) inhibitor p27 in coronary arterial smooth muscle cells. Objective: To
clarify the effect of BPS on HPASMC proliferation during hypoxic exposure, especially focusing
on the cell cycle regulation and expression of CDK inhibitor p27. Methods: HPASMC was
cultured in the presence/absence of BPS in hypoxic chamber. We estimated the proliferative
activity by bromodeoxyuridine (BrdU) incorporation and cell cycle analysis. In addition, we
evaluated the expression of CDK inhibitor, p27, in terms of protein and its mRNA. Results: We
found that proliferation of HPASMC was promoted by hypoxic condition, and BPS suppressed its
proliferation. Hypoxic condition decreased the expression of CDK inhibitor p27 whereas BPS up-
regulated both mRNA and protein expression of p27. Conclusion: The proliferation of HPASMC
is regulated by the expression of CDK inhibitor, p27.
