The Role of Angiotensin II and Prostaglandins in Arcade Formation in a Developing Microvascular Network

Abstract

There are basically two types of branching patterns in the terminal part of the arteriolar tree. On the one hand, in a number of tissues, including the developing chick embryo chorioallantoic membrane (CAM), the pattern is dichotomous, whereas in other tissues many arteriolar-arteriolar connections, arcades, are found. The structure of the branching pattern depends on the local physical and chemical environment. The goal of this study was to investigate whether substances with an effect on vascular growth influence the vascular branching pattern. We treated chick embryo CAMs daily from day 7 to day 14 postfertilization with 0.9% NaCl, angiotensin II (ANG-II), ANG-II in combination with different angiotensin receptor subtype antagonists, i.e., losartan and CGP 42112 A, or the prostaglandin synthesis inhibitor acetylsalicylic acid (ASA). Arcade formation was quantified by counting the number of arcades per cm² treated area, the branch-node ratio and mean surface area of arcade loops. ANG-II caused a 2-fold increase in the number of arcades versus 0.9% NaCl. Addition of ASA or losartan caused a further enhancement of arcade formation expressed in the number and branch-node ratio. CGP 42112A had no significant effect on arcade formation. From these data we hypothesize that ANG-II stimulates the process of capillary upgrading to arterioles by stimulation of arteriolar smooth muscle cell growth. Prostaglandins normally counteract this effect. After blockade of prostaglandin action, the ANG-II-induced arterialization is enhanced, resulting in pronounced arcade formation. The actions of losartan may be related to its inhibitory effects on prostaglandins rather than angiotensin receptor antagonism.

Angiotensinogen and Its Cleaved Derivatives Inhibit Angiogenesis

“…This is controversial because quinapril, an ACE inhibitor, increased rather than decreased vascular density in a model of acute limb ischemia in the rabbit. 27 The proangiogenic activity of Ang II was first demonstrated on the chicken CAM by Le Noble et al 28 and later in a sponge model by Machado et al 29 This angiogenic effect of the renin system on microvessels has been documented in a model of electrical stimulation-induced angiogenesis. 30 It may seem paradoxical that the same molecule, AGT, exhibits an antiangiogenic effect as a serpin and an angiogenic effect as the precursor of Ang II.…”

The potential role of angiotensin II in the vasculature

“…Le Noble and colleagues 47 reported that Ang II may not act by influencing endothelial cell proliferation and migration like most other angiogenic factors but that its primary target is the vascular smooth muscle. Ang II may act as a mitogen for vascular smooth muscle and enhance their anchoring in the vessel wall.…”

Involvement of angiotensin II type 2 receptor (AT2R) signaling in human pancreatic ductal adenocarcinoma (PDAC): a novel AT2R agonist effectively attenuates growth of PDAC grafts in mice

“…[13][14][15] Ang II-AT1R signaling also stimulates the expression of HIF-1a and VEGF, 16,17 signals that cause neovascularization and are required for solid tumor growth. 18,19 Ang II stimulates infiltration and activation of macrophages. 20,21 In addition, AT1R signaling is shown to be associated with cancer progressions and poor prognosis in various organ type cancers.…”