Kohno M, Yasunari K, Yokokawa K, Horio T, Ikeda M, Kano H, Minami M, Hanehira T, Yoskikawa J
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Hypertension. 1996 Mar;27(3 Pt 2):663-7. doi: 10.1161/01.hyp.27.3.663.
Adrenomedullin has recently been isolated from human pheochromocytoma. We designed the present study to examine the effect of adrenomedullin on the production of the vasoconstrictive and growth-promoting peptide endothelin-1 (ET-1) after stimulation with platelet-derived growth factor (PDGF) in cultured rat glomerular mesangial cells. PDGF stimulated ET-1 production in a concentration-dependent manner. Rat adrenomedullin inhibited this stimulated ET-1 production in a concentration-dependent manner between 10(-7) and 10(-8) mol/L. Rat adrenomedullin also increased the cellular level of cAMP in a concentration-dependent manner between 10(-7) and 10(-8) mol/L. Human adrenomedullin was less effective than rat adrenomedullin with respect to inhibiting ET-1 production and increasing cAMP levels. The addition of 8-bromo-cAMP (10(-3) and 10(-4) mol/L) reduced PDGF-induced ET-1 production. Furthermore, forskolin (10(-4) and 10(-5) mol/L), an activator of adenylate cyclase, reduced PDGF-induced ET-1 production. In contrast, the basal production of ET-1 was not significantly altered by rat and human adrenomedullin. These results indicate that adrenomedullin inhibits PDGF-induced ET-1 production in cultured rat mesangial cells, probably through a cAMP-dependent process.
肾上腺髓质素最近已从人嗜铬细胞瘤中分离出来。我们设计了本研究，以检测在培养的大鼠肾小球系膜细胞中，血小板衍生生长因子（PDGF）刺激后，肾上腺髓质素对血管收缩和促生长肽内皮素-1（ET-1）产生的影响。PDGF以浓度依赖的方式刺激ET-1的产生。大鼠肾上腺髓质素在10^(-7)至10^(-8) mol/L之间以浓度依赖的方式抑制这种刺激的ET-1产生。大鼠肾上腺髓质素在10^(-7)至10^(-8) mol/L之间也以浓度依赖的方式增加细胞内cAMP水平。就抑制ET-1产生和增加cAMP水平而言，人肾上腺髓质素的效果不如大鼠肾上腺髓质素。添加8-溴-cAMP（10^(-3)和10^(-4) mol/L）可降低PDGF诱导的ET-1产生。此外，腺苷酸环化酶激活剂福斯可林（10^(-4)和10^(-5) mol/L）可降低PDGF诱导的ET-1产生。相比之下，大鼠和人肾上腺髓质素对ET-1的基础产生没有显著影响。这些结果表明，肾上腺髓质素可能通过cAMP依赖的过程抑制培养的大鼠系膜细胞中PDGF诱导的ET-1产生。
