[Effect of adrenomedullin 1-50 on chronic hypoxic pulmonary hypertension in rats].
OBJECTIVE
To explore the effect of adrenomedullin(1-50) (ADM(1-50)) on hypoxic pulmonary hypertension and pulmonary vascular structural remodeling and the plasma concentration of nitric oxide (NO) and hydrogen sulfide (H(2)S) in rats.


METHODS
Twenty male Wistar rats were randomly divided into control group (n=7), hypoxic group (n=6) and hypoxic with ADM(1-50) group (n=7). ADM(1-50) was subcutaneously administered into rats of hypoxic with ADM(1-50) group by mini-osmotic pump (300 ng/h). After two weeks' hypoxic challenge, mean pulmonary arterial pressure (mPAP) was evaluated by using a right cardiac catheterization procedure. The ratio of right ventricular mass to left ventricular plus septal mass [RV/(LV+S)] was detected. Pulmonary vascular microstructure was measured and the ultrastructural changes in intra-acinar pulmonary arteries were observed. Meanwhile, plasma concentrations of NO and H(2)S were measured.


RESULTS
mPAP was significantly increased in hypoxic rats than that in controls [(24.9+/-6.8) mmHg vs (14.3+/-2.4) mmHg, P<0.01,1 mmHg=0.133 kPa]; RV/(LV+S) was also significantly increased in hypoxic rats than that in controls [(0.318+/-0.054) vs (0.182+/-0.007), P<0.01]. Microstructure and ultrastructure of pulmonary arteries changed obviously in hypoxic rats with the development of hypoxic pulmonary vascular structural remodeling. Meanwhile, plasma NO and H(2)S concentrations in hypoxic rats were markedly decreased compared with controls. However, mPAP was significantly decreased in hypoxic rats treated with ADM(1-50) than that in hypoxic rats [(14.9+/-3.0) mmHg vs (24.9+/-6.8) mmHg, P<0.01]; RV/(LV+S) was also significantly decreased than that in hypoxic rats [(0.185+/-0.011) vs (0.318+/-0.054), P<0.01]. ADM(1-50) ameliorated pulmonary vascular structural remodeling of hypoxic rats in association with an increase in plasma NO and H(2)S concentrations.


CONCLUSIONS
ADM(1-50) plays an important role in regulation of the development of hypoxic pulmonary hypertension and hypoxic pulmonary vascular structural remodeling, through promoting NO and H(2)S production in hypoxic rats.
Qi
Jian-guang
JG
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. qijianguang@sohu.com
Ding
Ya-guang
YG
Tang
Chao-shu
CS
Du
Jun-bao
JB
D053607:Adrenomedullin / Q000494:pharmacology*; D056151:Airway Remodeling; D000818:Animals; D002908:Chronic Disease; D006862:Hydrogen Sulfide / Q000097:blood; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D000860:Hypoxia / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D008168:Lung / Q000098:blood supply; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D010446:Peptide Fragments / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar
D010446:Peptide Fragments; C108043:adrenomedullin (1-50); D053607:Adrenomedullin; D009569:Nitric Oxide; D006862:Hydrogen Sulfide