Inhibition of expression of hypoxia-inducible factor-1alpha mRNA by nitric oxide in hypoxic pulmonary hypertension rats.
In order to study the effect of nitric oxide (NO) on the expression of hypoxia-inducible factor-1 alpha (HIF-1alpha) mRNA in hypoxic pulmonary hypertension (HPH) rats, 30 healthy male Wistar rats were randomly divided into normoxic control group, chronic hypoxic group and hypoxia plus L-arginine (L-Arg) group. The animal model of HPH was developed. The mean pulmonary arterial pressure (mPAP) was measured by inserting a microcatheter into the pulmonary artery. The HIF-1alpha mRNA expression levels were detected by in situ hybridization (ISH) and semiquantitative RT-PCR. It was found that after 14 days hypoxia, the mPAP in normoxic control group (17.6 +/- 2.7 mmHg, 1 mmHg=0.133 kPa) was significantly lower than that in chronic hypoxic group (35.8 +/- 6.1 mmHg, t=0.2918, P<0.05) and mPAP in chronic hypoxic group was higher than that in hypoxia plus L-arginine group (24.4 +/- 3.8 mmHg, t=0.2563, P<0.05). ISH showed that the expression of HIF-1alpha mRNA in the intraacinar pulmonary arteriolae (IAPA) in normoxic control group (0.1076 +/- 0.0205) was markedly weaker than that in chronic hypoxic group (0.3317 +/- 0.0683, t=3.125, P<0.05) and that in chronic hypoxic group was stronger than that in hypoxia plus L-arginine group (0.1928 +/- 0.0381, t=2.844, P<0.05). RT-PCR showed that the content of HIF-1alpha mRNA in chronic hypoxic group (2.5395 +/- 0.6449) was 2.16 times and 1.75 times higher than that in normoxic control group (1.1781 +/- 0.3628) and hypoxia plus L-arginine group (1.4511 +/- 0.3981), respectively. It is concluded that NO can reduce the mPAP by the inhibition of the expression of HIF-1alpha mRNA, which may be one of the mechanisms through which NO affects the pathogenesis of HPH.
Ao
Qilin
Q
Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030.
Huang
Lei
L
Zhu
Pengcheng
P
Xiong
Mi
M
Wang
Dixun
D
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D014157:Transcription Factors; D009569:Nitric Oxide; D001120:Arginine