Forty adult male Wistar rats were randomly divided into five groups: a control group (C group) and groups with
hypoxia for 3, 7, 14 and 21 days (H(3),
H(7), H(14), H(21) group), eight rats per group. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle
hypertrophy index (RVHI) were measured. Lungs were inflation fixed for in situ hybridization and immunohistochemistry.
RESULTS: mPAP increased significantly in
H(7) group [(18.41 +/- 0.37) mm Hg, 1 mm Hg = 0.133 kPa, P < 0.05], reaching its peak in H(14) group [(21.17 +/- 0.23) mm Hg], then remained at the high level.
Hypoxia induced pulmonary artery remodeling and right ventricle
hypertrophy index became evident in H(14) group. Expression of iNOS
protein in control group (0.109 +/- 0.021) was weakly positive in pulmonary arterial tunica media, while the level of iNOS
protein was markedly up-regulated in H(3) group (0.225 +/- 0.030, P < 0.01), reaching its peak in
H(7) group (0.312 +/- 0.036), then remained at the high level. Expression of iNOS
mRNA in C group (0.112 +/- 0.030) was weakly positive in pulmonary arterial wall, while the level of iNOS
mRNA was markedly up-regulated in H(3) group (0.245 +/- 0.036), reaching its peak in
H(7) group (0.318 +/- 0.034, P < 0.01), then remained at the high level. Expression of TGF-beta(1)
protein in C group (0.042 +/- 0.012) was weakly positive, but the level of TGF-beta(1)
protein was markedly up-regulated in H(3) group (0.198 +/- 0.031), reaching its peak in
H(7) group (0.267 +/- 0.035, P < 0.01), and then tended to decline in H(14) and H(21) group. TGF-beta(1)
mRNA staining was weakly positive in C group (0.145 +/- 0.018), H(3) group (0.163 +/- 0.021) and
H(7) group (0.176 +/- 0.026), but began to increase significantly in H(14) group (0.385 +/- 0.028, P < 0.01), and then remained stable. TGF-beta(1)
protein and
mRNA were located predominantly in tunica adventitia and tunica media. Linear correlation analysis showed that TGF-beta(1)
mRNA, iNOS
mRNA and
protein were positively correlated with mPAP, vessel morphometry and RVHI (r = 0.843 - 0.937, all P < 0.01). TGF-beta(1)
protein (tunica adventitia) was negatively correlated with iNOS
mRNA and
protein (r = -0.856, -0.835, all P < 0.01).
CONCLUSIONS: