[Effect of adrenomedullin on the regulation of pulmonary arterial pressure in hypoxic rats].
OBJECTIVE
To evaluate the effect of adrenomedullin (ADM) on pulmonary circulation and the change of ADM in plasma and lung tissue from rats with hypoxic pulmonary hypertension.


METHODS
Fifty Wistar rats were divided into the control group (10 rats) and the hypoxic group (40 rats). The animal model of pulmonary hypertension was established by exposing the rats to normobaric hypoxic conditions for 3 weeks; Mean pulmonary arterial pressure (mPAP) was measured by right cardiac catheterization, and mean systemic blood pressure (mSBP) was measured by left femoral catheterization. The thickness of pulmonary arterioles was measured by a computerized image analyser. The level of ADM in plasma and lung tissue was measured by radioimmunoassay. We ADM was administered in doses of 0.5, 1.0, 2.0 nmol/kg respectively to 30 hypoxic rats and the changes in mPAP and mSBP to ADM was evaluated.


RESULTS
Rats exposed to hypoxia developed pulmonary hypertension, the mPAP in the control group being (16 +/- 3) mm Hg and in hypoxic group being (30 +/- 4) mm Hg, and the difference was significant (P < 0.01). The hypoxic rats developed significantly thickened pulmonary arterioles. The plasma level of ADM was (288 +/- 24) pg/ml in the hypoxic rats and (168 +/- 25) pg/ml in the control group the difference being significant (P < 0.01). The level of ADM in the lung homogenates from the hypoxic group was (2 319 +/- 238) pg/g and that from the control group was (1 153 +/- 127) pg/g and the difference was significant (P < 0.01). The ADM levels had a positive correlation with the mPAP (gamma = 0.567 and 0.612 P < 0.01, respectively). Administration of exogenous ADM reduced the mPAP in a dose-dependent manner in hypoxic rats, and the effect lasted 5 approximately 15 minutes.


CONCLUSIONS
ADM has a relaxing effect on pulmonary circulation. The change of ADM in plasma and lung tissue may serve as a compensatory mechanism in maintaining the stability of pulmonary circulation in hypoxic condition.
Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.
Deyun
D
Cheng
Wei
W
Tian
Wenbin
W
Chen
Xinrong
X
Xiao
D053607:Adrenomedullin; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011651:Pulmonary Artery / Q000378:metabolism / Q000503:physiopathology*; D011652:Pulmonary Circulation; D051381:Rats; D017208:Rats, Wistar
D010455:Peptides; D053607:Adrenomedullin; D010100:Oxygen