Yoshihara F, Nishikimi T, Horio T, Yutani C, Takishita S, Matsuo H, Ohe T, Kangawa K
Research Institute, National Cardiovascular Center, Suita, Osaka, Japan.
Eur J Pharmacol. 1998 Aug 14;355(1):33-9. doi: 10.1016/s0014-2999(98)00475-0.
A novel vasorelaxant peptide, adrenomedullin, its messenger ribonucleic acid (mRNA), and the mRNA for its receptor are highly expressed in the lung, suggesting that adrenomedullin may play a role in the regulation of the pulmonary circulation. We investigated whether the chronic infusion of rat adrenomedullin would affect pulmonary hypertension and right ventricular hypertrophy produced by the administration of monocrotaline. Four-week-old male Wistar rats received a single subcutaneous injection of 60 mg/kg monocrotaline and were then chronically and subcutaneously infused with rat adrenomedullin (PH + AM group, n = 8) or saline (PH group, n = 10) by an osmotic minipump for a period of 21 days. Plasma levels of adrenomedullin were significantly higher in the PH vs. the control group. The chronic infusion of adrenomedullin in rats with pulmonary hypertension increased the plasma levels of adrenomedullin to a value 94% greater than that of the control group and 55% greater than that of the untreated PH group. Chronic infusion of adrenomedullin significantly lessened the increase in right ventricular systolic pressure and the ratio of right ventricular weight to body weight seen after monocrotaline treatment. Histological examination revealed that adrenomedullin also attenuated the medial thickening of the pulmonary artery. These results suggest that chronic infusion of adrenomedullin attenuates the pulmonary hypertension and right ventricular hypertrophy seen in rats treated with monocrotaline.
一种新型血管舒张肽——肾上腺髓质素、其信使核糖核酸（mRNA）及其受体的mRNA在肺中高度表达，这表明肾上腺髓质素可能在肺循环调节中发挥作用。我们研究了长期输注大鼠肾上腺髓质素是否会影响由给予野百合碱所产生的肺动脉高压和右心室肥厚。4周龄雄性Wistar大鼠接受单次皮下注射60mg/kg野百合碱，然后通过渗透微型泵长期皮下输注大鼠肾上腺髓质素（PH + AM组，n = 8）或生理盐水（PH组，n = 10），持续21天。与对照组相比，PH组血浆肾上腺髓质素水平显著更高。对患有肺动脉高压的大鼠长期输注肾上腺髓质素，可使血浆肾上腺髓质素水平升高，比对照组高94%，比未治疗的PH组高55%。长期输注肾上腺髓质素显著减轻了野百合碱治疗后右心室收缩压的升高以及右心室重量与体重之比。组织学检查显示，肾上腺髓质素还减轻了肺动脉中层增厚。这些结果表明，长期输注肾上腺髓质素可减轻野百合碱治疗大鼠出现的肺动脉高压和右心室肥厚。
