Repeated inhalation of adrenomedullin ameliorates pulmonary hypertension and survival in monocrotaline rats
Repeated inhalation of adrenomedullin ameliorates pulmonary hypertension and survival in monocrotaline rats
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DOI：
10.1152/ajpheart.00548.2002
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发表时间：
2003-11-01
影响因子：
4.8
通讯作者：
Kangawa, K
中科院分区：
文献类型：
--
作者：
Nagaya, N;Okumura, H;Kangawa, K
肾上腺髓质素（AM）是一种强有力的血管扩张肽。我们研究了雾化吸入AM是否能改善野百合碱（MCT）诱导的大鼠肺动脉高压。给予MCT的雄性Wistar大鼠（MCT大鼠）被分配接受AM（n = 8）或0.9%盐水（n = 8）的重复吸入。AM（5 μ g/kg）或生理盐水作为气雾剂使用超声雾化器吸入，每天4次，每次30分钟。吸入治疗3周后，AM组大鼠的平均肺动脉压和总肺阻力明显低于盐水组[平均肺动脉压：22 +/-2 vs. 35 +/-1 mmHg（-37%）;总肺阻力：0.048 +/-0.004 vs. 0.104 +/-0.006 www.example.com（-1）. min（-1）. kg（-1）（-54%，均P <0.01]。全身动脉压和心率均未改变。吸入AM可明显减轻MCT大鼠外周肺动脉中膜厚度的增加。Kaplan-Meier生存曲线显示，雾化吸入AM的MCT大鼠的生存率显著高于生理盐水组（6wk生存率分别为70%和10%，log-rank检验，P <0.01）。总之，反复吸入AM可抑制MCT诱导的肺动脉高压，而无全身性低血压，从而改善MCT大鼠的存活率。
Adrenomedullin (AM) is a potent vasodilator peptide. We investigated whether inhalation of aerosolized AM ameliorates monocrotaline (MCT)-induced pulmonary hypertension in rats. Male Wistar rats given MCT (MCT rats) were assigned to receive repeated inhalation of AM (n = 8) or 0.9% saline (n = 8). AM (5 mug/kg) or saline was inhaled as an aerosol using an ultrasonic nebulizer for 30 min four times a day. After 3 wk of inhalation therapy, mean pulmonary arterial pressure and total pulmonary resistance were markedly lower in rats treated with AM than in those given saline [mean pulmonary arterial pressure: 22 +/- 2 vs. 35 +/- 1 mmHg (-37%); total pulmonary resistance: 0.048 +/- 0.004 vs. 0.104 +/- 0.006 mmHg.ml(-1).min(-1).kg(-1) (-54%), both P < 0.01]. Neither systemic arterial pressure nor heart rate was altered. Inhalation of AM significantly attenuated the increase in medial wall thickness of peripheral pulmonary arteries in MCT rats. Kaplan-Meier survival curves demonstrated that MCT rats treated with aerosolized AM had a significantly higher survival rate than those given saline (70% vs. 10% 6-wk survival, log-rank test, P < 0.01). In conclusion, repeated inhalation of AM inhibited MCT-induced pulmonary hypertension without systemic hypotension and thereby improved survival in MCT rats.