An adrenomedullin fragment retains the systemic vasodepressor activity of rat adrenomedullin.
An adrenomedullin fragment retains the systemic vasodepressor activity of rat adrenomedullin.
复制标题
肾上腺髓质素片段保留了大鼠肾上腺髓质素的全身血管抑制活性。
DOI：
10.1016/0014-2999(94)90002-7
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发表时间：
1994
影响因子：
5
通讯作者：
Lippton,H
中科院分区：
文献类型：
--
作者：
Lin,B;Gao,Y;Chang,JK;Heaton,J;Hyman,A;Lippton,H
本研究旨在探讨人肾上腺髓质素（一种新发现的存在于正常人血浆中的肽）以及肾上腺髓质素片段对麻醉大鼠全身血流动力学的影响。静脉注射（i. v.）大剂量注射大鼠肾上腺髓质素、大鼠肾上腺髓质素-（11-50）、人肾上腺髓质素和人肾上腺髓质素-（13-52）以剂量依赖性方式降低平均全身动脉压。由于大鼠肾上腺髓质素和人肾上腺髓质素不降低心输出量，全身动脉压的降低反映了全身血管阻力的剂量依赖性降低。对相似剂量的肾上腺髓质素片段和它们各自的母体肾上腺髓质素肽的全身血管抑制反应是相似的。目前的数据表明，整个肾上腺髓质素分子是不需要的完整的全身血管扩张活性在体内表明，大鼠肾上腺髓质素-（11-50）或结构相似的肽，如果形成内源性，可以介导肾上腺髓质素在体内的血液动力学特性。由于大鼠肾上腺髓质素有显着更大的全身血管扩张活性比人肾上腺髓质素在大鼠相似的剂量，目前的数据表明，肾上腺髓质素有更大的全身血管扩张活性在其原生物种和有限的变化，肽的序列赋予显着不同的血管活性在体内。
The present study was undertaken to investigate the effects of human adrenomedullin, a newly discovered peptide present in normal human plasma, as well as a fragment of adrenomedullin, on systemic hemodynamics in the anesthetized rat. Intravenous (i.v.) bolus injections of rat adrenomedullin, rat adrenomedullin-(11–50), human adrenomedullin, and human adrenomedullin- (13–52) decreased mean systemic arterial pressure in a dose-dependent manner. Since rat adrenomedullin and human adrenomedullin did not decrease cardiac output, the decreases in systemic arterial pressure reflect dose-dependent reductions in systemic vascular resistance. The systemic vasodepressor responses to similar doses of the adrenomedullin fragments studied and to their respective parent adrenomedullin peptides were similar. The present data demonstrate that the entire adrenomedullin molecule is not required for full systemic vasodilator activity in vivo suggesting that rat adrenomedullin-(11–50) or a structurally similar peptide, if formed endogenously, could mediate the hemodynamic properties of adrenomedullin in vivo. Since rat adrenomedullin had significantly greater systemic vasodilator activity than human adrenomedullin at similar doses in the rat, the present data suggest that adrenomedullin has greater systemic vasodilator activity in its native species and that limited changes in the peptide's sequence confer markedly different vascular activity in vivo.