Shimosawa T, Kanozawa K, Nagasawa R, Mitarai T, Isoda K, Takahashi K, Ando K, Tozawa Y, Nagase M, Sasaki N, Fujita M, Takano K, Iiri T, Fujita T
Endocrine and Nephrology Department, University of Tokyo, Japan.
Hypertens Res. 2000 Mar;23(2):167-71. doi: 10.1291/hypres.23.167.
Adrenomedullin (AM) is a potent vasodilating peptide secreted from the vasculature of various organs. It is biologically active when its C-terminus is amidated. Recently, an RIA method was developed for measurement of the active form of AM, or mature AM. We here employed this method to investigate the significance of amidation of AM in controlling cardiovascular function. Thirty-six patients under hemodialysis were recruited and divided into hypertensive (n = 25; 157/86 mmHg) and normotensive (n= 11; 116/66 mmHg) groups. Mature AM, immature AM and blood pressure were monitored during hemodialysis in all patients. There was a significant reduction in blood pressure during hemodialysis in both groups, although after hemodialysis blood pressure was still higher in hypertensives than in normotensives (139 +/-14.8/76 +/- 2.5 mmHg vs. 110 +/- 5.1/66.7 +/- 3.1 mmHg). Mature AM before hemodialysis were lower in hypertensives than normotensives and it decreased in both groups. Although mature AM decreased more in normotensives than in hypertensives (-27 +/- 8% vs. -17 +/- 5%), at the end point, its level was still higher in normotensives. The ratio of mature AM/immature AM decreased only in normotensives (-11.4 8.7%), whereas it remained stable in hypertensives (0.2 +/- 5.6%). Both groups showed similar changes in ANP, endothelin, catecholamines, cGMP, and NOx. The low level in mature AM level in hypertensives may have contributed to the higher blood pressure in this group. The attenuation of AM amidation in normotensives indicates that an unspecified amidative enzyme of AM was regulated in order to normalize blood pressure.
肾上腺髓质素（AM）是一种由各种器官的血管分泌的强效血管舒张肽。当其C末端酰胺化时具有生物活性。最近，开发了一种放射免疫分析方法来测量AM的活性形式，即成熟AM。我们在此采用该方法研究AM酰胺化在控制心血管功能中的意义。招募了36名接受血液透析的患者，并将其分为高血压组（n = 25；157/86 mmHg）和血压正常组（n = 11；116/66 mmHg）。在所有患者血液透析期间监测成熟AM、未成熟AM和血压。两组在血液透析期间血压均显著降低，尽管血液透析后高血压患者的血压仍高于血压正常者（139±14.8/76±2.5 mmHg对110±5.1/66.7±3.1 mmHg）。高血压患者透析前的成熟AM低于血压正常者，且两组均降低。尽管成熟AM在血压正常者中的降低幅度大于高血压患者（-27±8%对-17±5%），但在终点时，其水平在血压正常者中仍较高。成熟AM/未成熟AM的比值仅在血压正常者中降低（-11.4±8.7%），而在高血压患者中保持稳定（0.2±5.6%）。两组在心房钠尿肽、内皮素、儿茶酚胺、环鸟苷酸和氧化氮方面显示出相似的变化。高血压患者成熟AM水平较低可能导致了该组血压较高。血压正常者中AM酰胺化的减弱表明，为了使血压正常化，AM的一种未明确的酰胺化酶受到了调节。
