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(Hypertension. 1995;25:744-747.)
© 1995 American Heart Association, Inc.

Articles

Endothelin-1 Enhances Nitric Oxide–Induced Cytotoxicity in Vascular Smooth Muscle

Takeshi Nakahashi; Keisuke Fukuo; Takuo Inoue; Shigeto Morimoto; Shigeki Hata; Mitsuo Yano; Toshio Ogihara

From the Department of Geriatric Medicine, Osaka University Medical School, and Tsukuba Research Institute, Banyu Pharmaceutical Co Ltd, Ibaraki (M.Y.), Japan.

Correspondence to Keisuke Fukuo, MD, Department of Geriatric Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan.

Abstract Prolonged incubation with 1 nmol/L interleukin-1 induced high levels of nitric oxide release and cytotoxicity in vascular smooth muscle cells. N^G-Monomethyl-L-arginine, an inhibitor of nitric oxide synthesis, inhibited interleukin-1–induced cytotoxicity at a concentration of 3 mmol/L. Furthermore, prolonged incubation with 0.1 mmol/L sodium nitroprusside, a nitric oxide donor, also induced cytotoxicity. On the other hand, endothelin-1 at concentrations from 10^-10 to 10^-7 mol/L induced a concentration-dependent enhancement of cytotoxicity induced by interleukin-1. However, endothelin-1 did not affect interleukin-1–induced nitric oxide production. Coculture study of vascular smooth muscle cells and endothelial cells without direct cell contact revealed that incubation for 72 hours with interleukin-1 induced high levels of nitric oxide release from cocultured vascular smooth muscle cells to the same degree as release from vascular smooth muscle cells alone. However, interleukin-1–induced cytotoxicity was more enhanced in cocultured vascular smooth muscle cells than in vascular smooth muscle cells alone. Furthermore, coincubation with 20 nmol/L BQ-485, an antagonist of one type of endothelin receptor (ET_A), prevented the enhancement of interleukin-1–induced cytotoxicity in cocultured vascular smooth muscle cells. These findings suggest that endothelin-1 secreted from endothelial cells may enhance nitric oxide–induced cytotoxicity by means of the ET_A receptor in vascular smooth muscle cells.

Key Words: nitric oxide • cytotoxins • muscle, smooth, vascular • endothelins • receptors, endothelin

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