Role of angiotensin II type 1 receptor in cerebral aneurysm formation in rats

Abstract

Abstract. Cerebral aneurysm (CA) causes catastrophic subarachnoid hemorrhage which is characterized by a high mortality and morbidity rate. CA is a common disease worldwide but to date there is no medical treatment against unruptured CAs. Thus, it is important to study the mechanisms of CA formation. Our previous report demonstrated that chronic inflammatory response in cerebral arterial bifurcation by hemodynamic stress deteriorated arterial walls and formed CA. Therefore, drugs with anti-inflammatory effects might effectively treat CA formation. As renin angiotensin system (RAS) is a major inflammatory cascade and related to various vascular diseases, including aortic aneurysms, the role of angiotensin (Ang) II type 1 receptor might contribute to the progression of CAs. However, in cerebral aneurysmal walls, Ang II type 1 receptor was not up-regulated. In addition, subcutaneously administered Ang II type 1 receptor blocker did not inhibit CA formation, nor inflammation in cerebral aneurysmal walls in rat models at a sub-suppressor dose. These results indicate that RAS might play a less important role in CA formation compared to aortic anuerysms or other vascular diseases. This suggests that there are different mechanisms between the pathogenesis of cereberal and aortic aneurysms.

Targeting the Angiotensin II Type 1 Receptor in Cerebrovascular Diseases: Biased Signaling Raises New Hopes

“…In an experimental model of aneurysm in rats combining a left internal carotid artery ligation with a left renal artery ligation and a high salt diet (to increase blood pressure), no change in AT 1 and ACE protein expression could be observed in cerebral aneurysmal walls. The authors therefore excluded any implication of AT 1 or ACE in cerebral aneurysm formation [38,39], as further supported by the lack of effect of an ARB treatment [38]. If not involved in the development of cerebral aneurysms, RAS has been proposed to play a pivotal role in their rupture.…”