Kohno M, Yokokawa K, Kano H, Yasunari K, Minami M, Hanehira T, Yoshikawa J
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Hypertension. 1997 Jun;29(6):1309-13. doi: 10.1161/01.hyp.29.6.1309.
The migration of coronary artery medial smooth muscle cells (SMCs) into the intima is proposed to be an important process of intimal thickening in coronary atherosclerotic lesions. In the current study, we examined the possible interaction of adrenomedullin, a novel vasorelaxant peptide, and angiotensin II (Ang II) on human coronary artery SMC migration using Boyden's chamber method. Ang II stimulated SMC migration in a concentration-dependent manner between 10(6) and 10(8) mol/L. This stimulation was clearly blocked by the Ang II type 1 receptor antagonist losartan but not by the type 2 receptor antagonist PD 123319. The migration stimulatory effect of Ang II was chemotactic in nature for cultured human coronary artery SMCs but was not chemokinetic. Human adrenomedullin clearly inhibited Ang II-induced migration in a concentration-dependent manner. Human adrenomedullin stimulated cAMP formation in these cells. Inhibition by adrenomedullin of Ang II-induced SMC migration was paralleled by an increase in the cellular level of cAMP. 8-Bromo-cAMP, a cAMP analogue, and forskolin, an activator of adenylate cyclase, inhibited the Ang II-induced SMC migration. These results suggest that Ang II stimulates SMC migration via type 1 receptors in human coronary artery and adrenomedullin inhibits Ang II-induced migration at least partly through a cAMP-dependent mechanism. Taken together with the finding that adrenomedullin is synthesized in and secreted from vascular endothelial cells, this peptide may play a role as a local antimigration factor in certain pathological conditions.
冠状动脉中层平滑肌细胞（SMC）向内膜迁移被认为是冠状动脉粥样硬化病变内膜增厚的一个重要过程。在本研究中，我们使用博伊登室法检测了新型血管舒张肽肾上腺髓质素与血管紧张素II（Ang II）对人冠状动脉SMC迁移的可能相互作用。Ang II在10⁻⁶至10⁻⁸mol/L之间以浓度依赖性方式刺激SMC迁移。这种刺激被1型Ang II受体拮抗剂氯沙坦明显阻断，但未被2型受体拮抗剂PD 123319阻断。Ang II的迁移刺激作用对培养的人冠状动脉SMC具有趋化性质，但不具有化学促动作用。人肾上腺髓质素以浓度依赖性方式明显抑制Ang II诱导的迁移。人肾上腺髓质素刺激这些细胞中cAMP的形成。肾上腺髓质素对Ang II诱导的SMC迁移的抑制作用与细胞内cAMP水平的升高平行。cAMP类似物8-溴-cAMP和腺苷酸环化酶激活剂福斯可林抑制Ang II诱导的SMC迁移。这些结果表明，Ang II通过人冠状动脉中的1型受体刺激SMC迁移，而肾上腺髓质素至少部分通过cAMP依赖性机制抑制Ang II诱导的迁移。结合肾上腺髓质素在血管内皮细胞中合成和分泌这一发现，该肽在某些病理条件下可能作为局部抗迁移因子发挥作用。
