Angiotensin-(1-7) inhibits in vitro endothelial cell tube formation in human umbilical vein endothelial cells through the AT(1-7) receptor

Angiotensin-(1-7) is increased in the circulation during human pregnancy, but its functional role is unknown. Recent studies suggested that it opposes angiotensin II mediated vascular growth. Because angiogenesis is critical to normal embryonic development during human pregnancy, this study assessed...

Full description

Saved in:
Bibliographic Details
Published in:Endocrine 2007-10, Vol.32 (2), p.212
Main Authors: Anton, Lauren, Merrill, David C, Neves, Liomar A A, Brosnihan, K Bridget
Format: Article
Language:English
Subjects:
Angiotensin I - pharmacology
Angiotensin II - analogs & derivatives
Angiotensin II - pharmacology
Angiotensin II Type 1 Receptor Blockers - pharmacology
Angiotensin Receptor Antagonists
Antihypertensive Agents - pharmacology
Cells, Cultured
Dose-Response Relationship, Drug
Endothelium, Vascular - cytology
Endothelium, Vascular - drug effects
Endothelium, Vascular - metabolism
Humans
Imidazoles - pharmacology
Losartan - pharmacology
Neovascularization, Physiologic - drug effects
Neovascularization, Physiologic - physiology
Peptide Fragments - pharmacology
Pyridines - pharmacology
Receptors, Angiotensin - physiology
Umbilical Veins - cytology
Umbilical Veins - drug effects
Umbilical Veins - metabolism
Vasoconstrictor Agents - pharmacology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Angiotensin-(1-7) is increased in the circulation during human pregnancy, but its functional role is unknown. Recent studies suggested that it opposes angiotensin II mediated vascular growth. Because angiogenesis is critical to normal embryonic development during human pregnancy, this study assessed the in vitro effects of angiotensin-(1-7) on human umbilical vein endothelial cell tube formation. The blocking effects of the angiotensin-(1-7) receptor antagonist, D-[Alanine7]-Ang-(1-7), and angiotensin II receptor AT1 and AT2 antagonists, losartan and PD123319, on tube formation were measured by counting tube branch points. Human umbilical vein endothelial cells were cultured in EGM-2 medium and treated with angiotensin-(1-7) (0.17 nM-17 microM) for 18 h. Angiotensin-(1-7) inhibited tube formation by 24% (P < 0.01) at all doses tested. Treatment with 1.7 microM angiotensin-(1-7) plus 17 microM D-[Alanine7]-Ang-(1-7) resulted in the reversal of angiotensin-(1-7) mediated inhibition of tube formation (P < 0.05). Losartan (17 microM) also reversed the angiotensin-(1-7) mediated inhibition of tube formation (P < 0.05). Tube formation was unaffected by PD123319. These results suggest that angiotensin-(1-7) has an anti-angiogenic effect on human umbilical vein endothelial cells through a unique AT(1-7) receptor that is sensitive to losartan, indicating that angiotensin-(1-7) may play an important role in the regulation of vascular growth in the placenta during pregnancy.
ISSN:1355-008X
1559-0100
DOI:10.1007/s12020-007-9022-1