Adrenomedullin as a novel antiproliferative factor of vascular smooth muscle cells

被引:183
作者
Kano, H
Kohno, M
Yasunari, K
Yokokawa, K
Horio, T
Ikeda, M
Minami, M
Hanehira, T
Takeda, T
Yoshikawa, J
机构
[1] First Department of Internal Medicine, Osaka City University, Medical School, Abeno-ku, Osaka 545
[2] Division of Hypertension and Atherosclerosis, First Department of Internal Medicine, Osaka City University Medical School, Abeno-ku, Osaka 545
关键词
adrenomedullin; cellular proliferation; cyclic AMP; vascular smooth muscle;
D O I
10.1097/00004872-199602000-00009
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Objective The present study was designed to examine whether adrenomedullin affects fetal calf serum (FCS)-stimulated proliferation in cultured rat vascular smooth muscle cells (VSMCs). Methods Rat VSMCs were grown from explants of Sprague-Dawley rat aorta and were grown using the standard cell culture method, After incubation for 24h with various concentrations of adrenomedullin in the presence of 5% FCS, trichloroacetic acid-insoluble tritiated thymidine was measured in a liquid scintillation counter, After incubation for 48 h, cell counts were performed, Cyclic adenosine 3',5'-monophosphate (AMP) levels were determined by radioimmunoassay, Results Rat adrenomedullin exhibited concentration-dependent inhibition of the FCS-stimulated increase in thymidine incorporation between 10(-7) and 10(-9) mol/l and of cell number at 10(-7) mol/l. However, the calcitonin gene-related peptide (CGRP) receptor antagonist human CGRP(8-37) abolished these antiproliferative effects of rat adrenomedullin, Inhibition by adrenomedullin of FCS-stimulated cellular proliferation was paralleled by an increase in the cellular level of cyclic AMP. 8-Bromocyclic AMP, a cyclic AMP analogue, and forskolin, an activator of adenylate cyclase, inhibited the FCS-stimulated increase in thymidine incorporation and cell number, Conclusions These results suggst that adrenomedullin inhibits FCS-stimulated proliferation in cultured rat VSMCs, probably through a cyclic AMP-dependent process, Taken together with the finding that adrenomedullin is synthesized in and secreted from vascular endothelial cells, adrenomedullin may play a role as an antiproliferative factor for VSMCs in a paracrine fashion.
引用
收藏
页码:209 / 213
页数:5
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