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[肾上腺髓质素1-50对大鼠慢性低氧性肺动脉高压的影响]

[Effect of adrenomedullin 1-50 on chronic hypoxic pulmonary hypertension in rats].

作者信息

Qi Jian-guang, Ding Ya-guang, Tang Chao-shu, Du Jun-bao

机构信息

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

出版信息

Beijing Da Xue Xue Bao Yi Xue Ban. 2006 Apr 18;38(2):151-4.

PMID:16617356
Abstract

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.

CONCLUSION

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.

摘要

目的

探讨肾上腺髓质素(1-50)(ADM(1-50))对大鼠低氧性肺动脉高压、肺血管结构重塑及血浆一氧化氮(NO)和硫化氢(H₂S)浓度的影响。

方法

将20只雄性Wistar大鼠随机分为对照组(n = 7)、低氧组(n = 6)和低氧+ADM(1-50)组(n = 7)。通过微型渗透泵对低氧+ADM(1-50)组大鼠皮下注射ADM(1-50)(300 ng/h)。经过两周的低氧刺激后,采用右心导管插入术评估平均肺动脉压(mPAP)。检测右心室质量与左心室加室间隔质量之比[RV/(LV+S)]。测量肺血管微观结构并观察腺泡内肺动脉的超微结构变化。同时,检测血浆NO和H₂S浓度。

结果

低氧大鼠的mPAP显著高于对照组[(24.9±6.8)mmHg对(14.3±2.4)mmHg,P<0.01,1 mmHg = 0.133 kPa];低氧大鼠的RV/(LV+S)也显著高于对照组[(0.318±0.054)对(0.182±0.007),P<0.01]。随着低氧性肺血管结构重塑的发展,低氧大鼠肺动脉的微观结构和超微结构发生明显变化。同时,低氧大鼠血浆NO和H₂S浓度与对照组相比显著降低。然而,用ADM(1-50)治疗的低氧大鼠的mPAP显著低于低氧大鼠[(14.9±3.0)mmHg对(24.9±6.8)mmHg,P<0.01];RV/(LV+S)也显著低于低氧大鼠[(0.185±0.011)对(0.318±

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