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(Hypertension. 1996;27:811-815.)
© 1996 American Heart Association, Inc.

Articles

Vascular Endothelial Growth Factor Suppresses C-Type Natriuretic Peptide Secretion

Kentaro Doi; Hiroshi Itoh; Yasato Komatsu; Toshio Igaki; Tae-Hwa Chun; Kazuhiko Takaya; Jun Yamashita; Mayumi Inoue; Takaaki Yoshimasa; Kazuwa Nakao

From the Department of Medicine and Clinical Science, Kyoto (Japan) University Graduate School of Medicine.

Correspondence to Hiroshi Itoh, MD, PhD, Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606, Japan. E-mail hiito@kuhp.kyoto-u.ac.jp.

Abstract Angiogenesis plays a pivotal role not only in wound healing and tumor progression but also in diabetic angiopathy, arteriosclerosis, and collateral formation of obstructive vascular diseases. Vascular endothelial growth factor (VEGF) is now thought to be an endothelium-specific and potent angiogenic factor. We previously demonstrated that C-type natriuretic peptide (CNP), originally isolated from porcine brain, is produced by endothelial cells and proposed that CNP can exert control over vascular tone and growth as a local vascular regulator. In the present study, we examined the effect of VEGF on CNP secretion from endothelial cells using the specific radioimmunoassay for CNP we developed. VEGF (1 to 100 ng/mL) dose-dependently suppressed CNP secretion from cultured bovine endothelial cells, and 100 ng/mL VEGF suppressed endothelial CNP secretion to 28% of control levels (31.7±5.5 versus 8.9±0.8 fmol/mL, vehicle versus VEGF). VEGF also suppressed CNP mRNA expression in endothelial cells 9 hours after administration. In contrast, basic fibroblast growth factor (20 ng/mL), an endothelium-nonspecific angiogenic factor, significantly stimulated CNP secretion by 290%. These results indicate that VEGF can regulate vascular tone and growth in the process of angiogenesis through suppression of endothelial secretion of CNP, which is an endothelium-derived vasorelaxing and growth-inhibitory peptide.

Key Words: natriuretic peptides • endothelial growth factors • endothelial cell • cell division

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