[The regulative effcets of A2a adenosine receptor on expression of SOCS-3 in rats of hypoxic pulmonary hypertension].
OBJECTIVE
To study the regulative effects and mechanism of A2aAR on expression of suppressor of cytokinesignaling-3(SOCS-3) in hypoxic pulmonary hypertension rats.


METHODS
Sprague-Daeley rats were randomly divided into 3 groups: a normal control group, a hypoxia group, and a hypoxia with selective agonists of A2aAR group. Animals in the hypoxia groups were housed in a chamber with 8%- 11% O2 and 1%-3% CO2 for 8 hours (8: 00 AM to 4: 00 PM) daily for 28 days. They were treated intraperitoneally with either 4 ml/kg weight of normal saline or 0.2 mg/kg weight of CGS-21680 30 minutes before exposure to hypoxia. Four weeks later, mean pulmonary artery pressure (mPAP), mean carotid arterial pressure (mCAP) and right ventricular rate [RV/(LV+ S)] were measured. The expression of A2aAR and SOCS-3 in pulmonary arterioles was measured by immunohistochemistry. The expression of A2aAR mRNA and SOCS-3 mRNA in lung tissues were measured by real time RT-PCR. The expression of A2aAR protein and SOCS-3 protein in lung tissues were measured by Western blot.


RESULTS
The mPAP in the hypoxia group was [(20.9±3.9)mmHg, 1 mmHg=0.133 kPa], significantly higher than the normal control group [(12.6±6.6)mmHg](P<0.01). The mPAP in CGS-21680 group was [ (14.8±3.8)mmHg], significantly lower than the hypoxia group(P<0.01). RV/(LV+ S) in the hypoxia group was [(35.2±2.0)%] , significantly higher than the normal control group [(29.6±2.7)%] (P<0.01). RV/(LV+ S) in the CGS-21680 group was [(28.3±8.8)%], significantly lower than the hypoxia group(P<0.01). WA/TA in the hypoxia group was (73±5, P<0.01), significantly higher than the normal control group. WA/TA in CGS21680 group was (54±3, P<0.01), significantly lower than the hypoxia group. A2aAR and SOCS-3 expressions on pulmonary arterioles in the hypoxia group were (0.134±0.034) and (0.119±0.011), both significantly higher than the normal group(P<0.01); and CGS-21680 treatment further increased their expressions. The mRNA expression of both molecules showed a 1.5-fold increase after 28-day hypoxia exposure. A2aAR activation by CGS-21680 treatment in hypoxia-exposed rats further increased the expression levels of A2aAR and SOCS-3 to about 2-fold higher than the normal controls. Furthermore, protein levels of A2aAR and SOCS-3 in the lung tissue were determined using Western blot. A similar increase was observed in hypoxia-induced pulmonary hypertension, and CGS-21680 treatment group showed the highest levels of these 2 proteins.


CONCLUSIONS
A2aAR activation prevents hypoxia-induced pulmonary hypertension, and its mechanisms are related to the activation of A2aAR SOCS-3 signaling pathway.
Department of Respiratory Medicine, Jiangdu People's Hospital, Yangzhou 225200, China.
R
R
Fan
X Y
XY
Huang
K Y
KY
Du
Y F
YF
Fan
L X
LX
Wang
D058908:Adenosine A2 Receptor Agonists / Q000008:administration & dosage; D000818:Animals; D062186:Arterial Pressure; D001160:Arterioles / Q000378:metabolism; D006352:Heart Ventricles; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D008168:Lung / Q000098:blood supply; D012333:RNA, Messenger; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D043683:Receptors, Adenosine A2 / Q000378:metabolism*; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000378:metabolism*
D058908:Adenosine A2 Receptor Agonists; D012333:RNA, Messenger; D043683:Receptors, Adenosine A2; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein