CYTOKINE-INDUCED C-TYPE NATRIURETIC PEPTIDE (CNP) SECRETION FROM VASCULAR ENDOTHELIAL-CELLS - EVIDENCE FOR CNP AS A NOVEL AUTOCRINE PARACRINE REGULATOR FROM ENDOTHELIAL-CELLS

We previously demonstrated that C-type natriuretic peptide (CNP), orig inally isolated from the porcine brain, is produced by endothelial cel ls and proposed that CNP can exert local control over vascular tone an d growth as a local regulator from endothelial cells. Since cytokines play pivotal roles in the control of vascular tone and structure, we h ave examined effects of various cytokines on CNP secretion from endoth elial cells using the specific radioimmunoassay for CNP. While interle ukin (IL)-2 had no significant effect on CNP secretion, IL-1alpha, IL- 1beta and tumor necrosis factor (TNF)-alpha stimulated CNP secretion i n a time- and dose-dependent manner. Among them', TNF-alpha, one of th e key mediators for inflammation and vascular remodeling, induced more than two orders of magnitude increase in CNP secretion. In addition, lipopolysaccharide (LPS) potently stimulated CNP secretion. These resu lts indicate that IL-1, TNF-alpha and LPS, the endotoxin itself, can r egulate local vascular tone and growth through the activation of CNP s ecretion from endothelial cells. Therefore, CNP could be of clinical r elevance as an autocrine/paracrine regulator from endothelial cells fo r systemic and local cytokine-associated disorders, such as endotoxin shock and atherosclerosis.