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 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.
Anton
Lauren
L
Hypertension and Vascular Research Center, Medical Center Boulevard, Wake Forest University School of Medicine, Winston-Salem, NC, 27157-1032, USA.
Merrill
David C
DC
Neves
Liomar A A
LA
Brosnihan
K Bridget
KB
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
C092006:7-Ala-angiotensin (1-7); D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C073402:PD 123319; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan