Adrenomedullin amidation enzyme activities in hypertensive patients

Adrenomedullin (AM) is a potent vasodilating peptide secreted from the vasc ulature of various organs. It is biologically active when its C-terminus is amidated. Recently, an RIA method was developed for measure ment of the ac tive 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 hyp ertensive (n = 25; 157/86 mmHg) and normotensive (n = 11; 116/66 mmHg) grou ps. Mature AM, immature AM and blood pressure were monitored during hemodia lysis in all patients. There was a significant reduction in blood pressure during hemodialysis in both groups, although after hemodialysis blood press ure was still higher in hypertensives than in normotensives (139 +/- 14.8/7 6 +/- 2.5 mmHg vs. 110 +/- 5.1/66.7 +/- 3.1 mmHg). Mature AM before hemodia lysis were lower in hypertensives than normotensives and it decreased in bo th groups. Although mature AM decreased more in normotensives than in hyper tensives (-27 +/- 8% vs. -17 +/- 5%), at the end point, its revel 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 hypertens ives (0.2 +/- 5.6%). Both groups showed similar changes in ANP, endothelin, catecholamines, cGMP, and NOx. The low level in mature AM level in hyperte nsives 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.