Glycine-extended adrenomedullin exerts vasodilator effect through amidation in the rat aorta

被引:16
作者
Cao, YN
Kitamura, K
Ito, K
Kato, J
Hashida, S
Morishita, K
Eto, T
机构
[1] Miyazaki Med Coll, Dept Internal Med 1, Miyazaki 8891692, Japan
[2] Minami Kyusyu Univ, Dept Food Sci & Technol, Miyazaki, Japan
[3] Miyazaki Med Coll, Dept Biochem, Miyazaki 8891692, Japan
关键词
adrenomedullin; glycine-extended adrenomedullin; amidation; vasorelaxant;
D O I
10.1016/S0167-0115(03)00002-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Human adrenomedullin (hAM) is an endogenous peptide that has potent vasodilator activity. Mature AM is biosynthesized from its intermediate form, glycine-extended AM (AM-gly), by carboxy-terminal amidation. AM-gly is generally considered to be biologically inactive but is a major molecular form in human and rat plasma. The present study demonstrated that recombinant human AM-gly (hAM-gly) elicits potent vasodilator effect on isolated rat aorta. In aortic rings, hAM-gly produced dose-dependent (0.1-100 nM) relaxation in phenylephrine-precontracted strips (pD(2) 8.4 +/- 0.5). The vasorelaxant potency of hAM-gly was comparable to that of hAM (pD(2) 8.6 +/- 0.2) but hAM-gly took a significantly (P< 0.01) longer time to reach the maximal relaxation compared with hAM (T-max 23 +/- 4 vs. 5 +/- 2 min). Vasorelaxant responses to hAM-gly were abolished by endothelial removal. N-ω-nitro-L-arginine (L-NNA) and AM(22-52) significantly (P < 0.01) reduced the vasodilator effect of hAM-gly. Furthermore, 4-phenyl-3-butenoic acid (PBA), an alpha-amidation enzyme inhibitor, significantly (P < 0.05) inhibited the vasorelaxant responses to hAM-gly without any effect on the hAM-induced relaxation, suggesting the possible process of amidation in the rat aorta. We further clarified that the aorta has the ability to convert exogenous hAM-gly to mature hAM and the conversion is inhibited by PBA. These results suggest that the circulating AM-gly may play a role in regulating vascular tone and increased plasma AM-gly may be involved in the pathophysiology of cardiovascular diseases. (C) 2003 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:109 / 114
页数:6
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