at 4383 m, and at 4, 8, 12, and 24 hours later. There was a significant increase in the average
breath condensate concentration of VEGF with L-arginine treatment over the 24 hour period.
There was also a significant increase in the average blood concentration of EPO, heart rate, and
Lake Louise Scores at specific time points at altitude, but no effect of L-arginine on these
measures. We conclude that L-arginine supplementation increases VEGF production in breath
condensates, but that this increase has no effect on other physiological measures or subjective
symptoms at altitude. Our findings suggest that L-arginine supplementation increases HIF-1
stabilization in the lung most likely through a NO-dependent pathway.
232.
CORTICOTROPIN-RELEASING FACTOR RECEPTOR TYPE 1 AND 2 MRNA
EXPRESSION IN THE RAT ANTERIOR PITUITARY IS MODULATED BY
INTERMITTENT HYPOXIA COLD AND RESTRAINT. Tong-Ying Wang
1
, Xue-Qun Chen
1
,
Ning-Yi Xu
1
, Ji-Zeng Du
1
, W.W Vale
2
, Chuan-Bao Wei
3
. Zhejiang
1
, Clayton
2
, Zhejiang
University
3
.
We had previously demonstrated that continual-hypoxia stimulated corticotropin-releasing
factor (CRF) release and CRF mRNA in hypothalamus, and enhanced plasma ACTH as well as
corticosterone of rats. This study demonstrated that CRF receptor 1 (CRF R1) and CRF receptor 2
(CRF R2) mRNA in the rat anterior pituitary changed by an intermittent hypoxia, cold, restraint
and in combination, using in situ autoradiograph. Rats were exposed to simulated intermittent
altitude hypoxia for 4h/d for various periods in a hypobaric chamber. The hypoxia of 2km (16.0%
O2) or 5km (10.8% O2) caused both CRF R1 and R2 mRNA change, with biphasic manner, a
significant decline for 1d and an enhancement after 2d. CRF R2 mRNA at 5km for 1d was
markedly decreased and increased for 2d, 5d. 5km hypoxia reduced markedly body weight gain.
The increased CRF R1 mRNA was induced by restraint, intermittent hypoxia, hypoxia+restraint
and hypoxia+cold respectively except for sole cold. The CRF R2 mRNA was significantly
increased by all the stresses. These results suggest: (1) CRF R1 and R2 mRNA in pituitary were
acutely and chronicly modulated with bi-phase manner by intermittent hypoxia, and were acutely
regulated by cold, intermittent hypoxia, restraint, cold+hypoxia and restraint+hypoxia (2) Both
CRF R1 and R2 mRNA were involved in activation of pituitary-adrenal cortex by these paradigm
stress; (3) The significant difference of CRF R1 mRNA expression in pituitary caused by
restraint, intermittent hypoxia and cold might suggest a different role in behavior. * This work is
supported by the grant from NSFC (Major Project No. 30393134 and Project No. 30070289;
30270232).
233.
EXPRESSIONS OF COCL2-INDUCED IMMUNOREACTIVE HYPOXIA-INDUCIBLE
FACTOR-1ALPHA INSULIN-LIKE GROWTH FACTOR AND INSULIN-LIKE GROWTH
FACTOR BINDING PROTEIN IN LIVER OF OCHOTONA CURZONIAE; MICROTUS
OECONOM. Shi-Jun Wang
1
, Xue-Qun Chen
1
, Ji-Zeng Du
1
, Cunming Duan
2
. Zhejiang Univ.
1
,
University of Michigan
2
.
Ochotona curzoniae and microtus oeconomus are native mammals to Tibetan plateau. The
response of HIF-1a, IGF-1 and IGF-BP of these mammals to hypoxia is unclear. Hypoxic
exposure was performed using an injection of CoCl2 (20, 40 and 60 mg/kg). Immunoreactive
proteins of HIF-1a, IGF-1 and IGF-BP were determined by in situ immunohistochemistry and
Western blot. The results showed: 1. CoCl2 markedly increased HIF-1a expression in mice liver
via i.p. an injection of 20 mg/kg, which trended to reduction with increased dosage of CoCl2.
CoCl2 only at 60 mg/kg significantly increased HIF-1a in Microtus oeconomus, however CoCl2
had no significant role in HIF-1a in Ochotona curzoniae. 2. CoCl2 significantly and dose-
dependently increased liver IGF-1 expression in Microtus oeconomus, but not in O. curzoniae
and mice. 3. CoCl2 induced a significant increase of liver IGFBP-1 in mice, which was reduced
with increased dosages of CoCl2, and no change of IGFBP-1 in M.oeconomus was showed.
However, a dramatic increase of IGFBP-1 levels was caused by the all doses of CoCl2. 4. CoCl2
40 mg/kg-induced IGFBP-1 increase initiated 6 h after injection and still high at 12 h in O.
