Mechanisms of angiotensin-(1-7)-induced inhibition of angiogenesis

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2001-04, Vol.280 (4), p.994-R1000
• Main Authors: Machado, R. D. P, Santos, R. A. S, Andrade, S. P
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Angiogenesis Inhibitors - pharmacology; Angiotensin I - pharmacology; Angiotensin II - analogs & derivatives; Angiotensin II - pharmacology; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents - pharmacology; Imidazoles - pharmacology; Losartan - pharmacology; Male; Mice; Neovascularization, Pathologic - prevention & control; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Peptide Fragments - pharmacology; Prostheses and Implants; Pyridines - pharmacology; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.2001.280.4.r994

Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil 31270-901 Angiotensin-(1-7) [ANG-(1-7)], an endogenous bioactive peptide constituent of the renin-angiotensin system, acts as an inhibitory growth factor in vitro and in vivo. In this study, we evaluated whether the antiangiogenic effect of ANG-(1-7) in the mouse sponge model of angiogenesis might be receptor mediated and involved in the release of nitric oxide (NO). The hemoglobin content (µg/mg wet tissue) of 7-day-old sponge implants was used as an index of the vascularization and showed that daily injections of ANG-(1-7) (20 ng) inhibited significantly the angiogenesis in the implants relative to the saline-treated group. The specific receptor antagonist D -Ala 7 -ANG-(1-7); A-779 prevented ANG-(1-7)-induced inhibition of angiogenesis. The antiangiogenic effect was also abolished by pretreatment with NO synthase inhibitors aminoguanidine (1 mg/ml) or N G -nitro- L -arginine methyl ester (0.3 mg/ml). Selective AT 1 and AT 2 angiotensin-receptor antagonists and an angiotensin-converting enzyme inhibitor, in combination with ANG-(1-7) or alone, did not alter angiogenesis in the implants. These results establish that the regulation of the vascular tissue growth by ANG-(1-7) is associated with NO release by activation of an angiotensin receptor distinct from AT 1 and AT 2 . mechanism; specific antagonist