Advertisement

Research Article Free access | 10.1172/JCI117557

Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P.

M Ziche, L Morbidelli, E Masini, S Amerini, H J Granger, C A Maggi, P Geppetti, and F Ledda

Department of Pharmacology, University of Florence, Italy.

Find articles by Ziche, M. in: PubMed | Google Scholar

Department of Pharmacology, University of Florence, Italy.

Find articles by Morbidelli, L. in: PubMed | Google Scholar

Department of Pharmacology, University of Florence, Italy.

Find articles by Masini, E. in: PubMed | Google Scholar

Department of Pharmacology, University of Florence, Italy.

Find articles by Amerini, S. in: PubMed | Google Scholar

Department of Pharmacology, University of Florence, Italy.

Find articles by Granger, H. in: PubMed | Google Scholar

Department of Pharmacology, University of Florence, Italy.

Find articles by Maggi, C. in: PubMed | Google Scholar

Department of Pharmacology, University of Florence, Italy.

Find articles by Geppetti, P. in: PubMed | Google Scholar

Department of Pharmacology, University of Florence, Italy.

Find articles by Ledda, F. in: PubMed | Google Scholar

Published November 1, 1994 - More info

Published in Volume 94, Issue 5 on November 1, 1994
J Clin Invest. 1994;94(5):2036–2044. https://doi.org/10.1172/JCI117557.
© 1994 The American Society for Clinical Investigation
Published November 1, 1994 - Version history
View PDF
Abstract

We evaluated the effects of nitric oxide (NO) generators and endogenous production of NO elicited by substance P (SP) in the angiogenesis process. Angiogenesis was monitored in the rabbit cornea in vivo and in vitro by measuring the growth and migration of endothelial cells isolated from coronary postcapillary venules. The angiogenesis promoted in the rabbit cornea by [Sar9]-SP-sulfone, a stable and selective agonist for the tachykinin NK1 receptor, and by prostaglandin E1 (PGE1), was potentiated by sodium nitroprusside (SNP). Conversely, the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), given systemically, inhibited angiogenesis elicited by [Sar9]-SP-sulfone and by PGE1. Endothelial cells exposed to SNP exhibited an increase in thymidine incorporation and in total cell number. Exposure of the cells to NO generating drugs, such as SNP, isosorbide dinitrate, and glyceryl trinitrate, produced a dose-dependent increase in endothelial cell migration. Capillary endothelial cell proliferation and migration produced by SP were abolished by pretreatment with the NO synthase inhibitors N omega-mono-methyl-L-arginine (L-NMMA), N omega-nitro-L-arginine (L-NNA), and L-NAME. Exposure of the cells to SP activated the calcium-dependent NO synthase. Angiogenesis and endothelial cell growth and migration induced by basic fibroblast growth factor were not affected by NO synthase inhibitors. These data indicate that NO production induced by vasoactive agents, such as SP, functions as an autocrine regulator of the microvascular events necessary for neovascularization and mediates angiogenesis.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

Version history
  • Version 1 (November 1, 1994): No description
Advertisement
Advertisement