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Aims – Based on the high vascular activity of angiotensin II receptor subtype 1 and 2 (AT1R
und AT2R), this study pursued the objective to investigate the influence of both receptors on cerebral collateral growth in rats. Additionally, the arteriogenic potential of the kallikreinkinin system (KKS) was to be analyzed. In particular, its interface with the renin-angiotensin system (RAS), namely the angiotensin-converting-enzyme (ACE), had to be considered.
Methods – Three vessel occlusion (3-VO) is an animal model inducing an enlargement of collateral arteries in the Circle of Willis through bilateral occlusion of the vertebral arteries and the left common carotid artery. During the first part of this study, rats that underwent 3-VO were treated with an AT1R antagonist or an AT2R agonist for three weeks. In the second part, animals were treated with an angiotensin-converting-enzyme (ACE) inhibitor for seven days. Another group was treated with ACE inhibitor as well as bradykinin receptor inhibitors (BRB). The resulting effects were analyzed by measurement of cerebrovascular reserve capacity (CVRC), latex angiography and immunohistochemical staining.
Results – The present study is a first-time demonstration of the effects of a modulation of RAS and KKS on cerebral arteriogenesis in normotensive rats. In the first part, CVRC measurement and latex angiography did not reveal any significant differences between treatment with AT1R antagonist, AT2R agonist and control. In the second part, the application of ACE inhibitor (10 ± 9 %) as well as the application of ACE inhibitor and BRB (11 ± 5 %) led to a significant enhancement of the CVRC compared to control (2 ± 7 %). Furthermore, diameters of the ipsilateral posterior cerebral artery of both groups (ACE inhibitor: 244 ± 18 μm; ACE inhibitor and BR inhibitors: 274 ± 20 μm) were significantly increased compared to control (212 ± 10 μm). Accordingly, immunohistochemical staining revealed significantly more vascular smooth muscle layers, whereas single ACE inhibition led to fewer cells in a proliferative state.
Conclusion – This study demonstrated that a modulation of AT1R and AT2R has no influence on cerebral arteriogenesis. In contrast, ACE inhibition is a stimulating factor which is not abolished by application of BRB though. Hence, this aspect is still deeply interesting for the development of biological bypasses.