Angiotensin II regulation of ovine fetoplacental artery endothelial functions: interactions with nitric oxide

Abstract

During normal pregnancy, elevated angiotensin II (Ang II) concentrations in the maternal and fetal circulations are associated with dramatic increases in placental angiogenesis and blood flow. Much is known about a local renin-angiotensin system within the uteroplacental vasculature. However, the roles of Ang II in regulating fetoplacental vascular functions are less well defined. In the fetal placenta, the overall in vivo vasoconstrictor responses of the blood vessels to Ang II infusion is thought to be less than that in its maternal counterpart, even though infused Ang II induces vasoconstriction. Recent data from our laboratories suggest that Ang II stimulates cell proliferation and increases endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO) in ovine fetoplacental artery endothelial cells. These data imply that elevations of the known vasoconstrictor Ang II in the fetal circulation may indeed play a role in the marked increases in fetoplacental angiogenesis and that Ang II-elevated endothelial NO production may partly attenuate Ang II-induced vasoconstriction on vascular smooth muscle. Together with both of these processes, the high levels of Ang II in the fetal circulation may serve to modulate overall fetoplacental vascular resistance. In this article, we review currently available data on the expression of Ang II receptors in the ovine fetal placenta with particular emphasis on the effects of Ang II on ovine fetoplacental endothelium. The potential cellular mechanisms underlying the regulation of Ang II on endothelial growth and vasodilator production are discussed.

Impaired placental neovascularization in mice with pregnancy-associated hypertension

“…23,41,43 On the other hand, angiotensin-II was reported to increase total eNOS protein in ovine fetoplacental arteryderived ECs. 44 Therefore, concurrent downregulation of eNOS mRNA with apelin/APJ mRNAs in PAH placenta under excessive angiotensin-II needs further investigation. Claudin-5 belongs to tight junction molecules and contributes to cell-cell adhesion in ECs.…”

Dynamic changes in messenger RNA profiles of bovine endometrium during the oestrous cycle

“…Genes with higher mRNA levels during the luteal phase, which are more directly involved in angiogenesis are ephrin-A1 (EFNA1), endothelial differentiation sphingolipid G-protein-coupled receptor, 3 (EDG3), angiotensinogen (AGT), endothelial PAS domain protein 1 (EPAS1; hypoxia-inducible factor 2-a) and Kruppel-like factor 5 (KLF5; clusters 1, 1, 2, 1, 2). AGT codes for the progenitor of angiotensin II, which has been described to function as a vasoconstrictor and to regulate fetoplacental angiogenesis in the ovine placenta (Zheng et al 2005). EPAS1 and KLF5 code for transcription factors controlling the expression of vascular endothelial growth factor (VEGF ), VEGF receptor 1 (FLT1), VEGF receptor 2 (KDR), and TEK (Takeda et al 2004) and of platelet-derived growth factor (PDGF ), early growth response 1, (EGR1), plasminogen activator inhibitor type 1 (SERPINE1), inducible nitric oxide synthase 2A (NOS2A), and VEGF receptor genes (Nagai et al 2005), respectively.…”

Angiotensin II promotes NO production, inhibits apoptosis and enhances adhesion potential of bone marrow-derived endothelial progenitor cells

“…AngII inhibits EC apoptosis [6], upregulates adhesion molecules [7] and potently augments endothelial nitric oxide synthase (eNOS) mRNA expression, which thereby increases nitric oxide (NO) release [8]. Therefore, we propose that AngII may have similar effects on EPCs as well.…”