Nagaya Noritoshi, Kangawa Kenji
Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujisjirodai, Suita, Osaka 565-8565, Japan.
Peptides. 2004 Nov;25(11):2013-8. doi: 10.1016/j.peptides.2004.07.007.
Adrenomedullin (AM) is a potent, long-lasting pulmonary vasodilator peptide. Plasma AM level is elevated in patients with primary pulmonary hypertension (PPH), and circulating AM is partially metabolized in the lungs. These findings suggest that AM plays an important role in the regulation of pulmonary vascular tone and vascular remodeling. We have demonstrated the effects of three types of AM delivery systems: intravenous administration, inhalation, and cell-based gene transfer. Despite endogenous production of AM, intravenously administered AM at a pharmacologic level decreased pulmonary vascular resistance in patients with PPH. Inhalation of AM improved hemodynamics with pulmonary selectivity and exercise capacity in patients with PPH. Cell-based AM gene transfer ameliorated pulmonary hypertension rats. These results suggest that additional administration of AM may be effective in patients with pulmonary hypertension. AM may be a promising endogenous peptide for the treatment of pulmonary hypertension.
肾上腺髓质素（AM）是一种强效、长效的肺血管舒张肽。原发性肺动脉高压（PPH）患者的血浆AM水平升高，且循环中的AM在肺中会部分代谢。这些发现表明，AM在肺血管张力调节和血管重塑中起重要作用。我们已经证明了三种AM递送系统的效果：静脉内给药、吸入和基于细胞的基因转移。尽管内源性产生AM，但在药理学水平静脉内给予AM可降低PPH患者的肺血管阻力。吸入AM可改善PPH患者的血流动力学，具有肺选择性并提高运动能力。基于细胞的AM基因转移改善了肺动脉高压大鼠的病情。这些结果表明，额外给予AM可能对肺动脉高压患者有效。AM可能是一种有前景的内源性肽，可用于治疗肺动脉高压。
