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(Hypertension. 1996;27:663-667.)
© 1996 American Heart Association, Inc.

Articles

Interaction of Adrenomedullin and Platelet-Derived Growth Factor on Rat Mesangial Cell Production of Endothelin

Masakazu Kohno; Kenichi Yasunari; Koji Yokokawa; Takeshi Horio; Miwako Ikeda; Hiroaki Kano; Mieko Minami; Takao Hanehira; Junichi Yoshikawa

From the First Department of Internal Medicine, Osaka City (Japan) University Medical School.

Correspondence to Masakazu Kohno, MD, Division of Hypertension and Atherosclerosis, First Department of Internal Medicine, Osaka City University Medical School, 1-5-7 Asahi-machi, Abeno-ku, Osaka 545, Japan.

Abstract 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.

Key Words: adrenomedullin • endothelin • platelet-derived growth factor • mesangium, glomerular • peptides

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