Effects of intracerebroventricular infusion of angiotensin-(1-7) on bradykinin formation and the kinin receptor expression after focal cerebral ischemia-reperfusion in rats

Accumulating evidence suggests that the angiotensin-(1-7) [Ang-(1-7)], is an active member of the brain renin-angiotensin system (RAS). We evaluated the possibility that intracerebroventricular (ICV, lateral ventricle) infusion of exogenous Ang-(1-7) could participate in the potentiation of bradykinin (BK) release and the kinin receptor expression in ischemic brain parenchyma after focal cerebral ischemia-reperfusion in rats. The middle cerebral artery occlusion (MCAO) and sham-operated models were prepared, continuously administrated with Ang-(1-7) or artificial cerebro spinal fluid (aCSF) by implanted Alzet osmotic minipumps into lateral cerebral ventricle after reperfusion in male Sprague-Dawley (SD) rats. Experimental animals were divided into sham-operated group (sham+aCSF), aCSF treatment group (MCAO+aCSF) and Ang-(1-7) treatment groups [MCAO+Ang-(1-7)] at low (1 pmol/0.5 mu l/h), medium (100 pmol/0.5 mu l/h) or high (10 nmol/0.5 mu l/h) dose levels. Cerebral infarction resulted in a significant increase of BK formation from 3 h to 6 h compared with sham-operated group after reperfusion, whereas medium- and high-dose Ang-(1-7) infusion markedly enhanced BK levels from 6 h to 48 h after reperfusion. Medium- and high-dose Ang-(1-7) infusion markedly increased kinin B-2 receptor mRNA and protein expression, whereas only high-dose Ang-(1-7) infusion induced upregulating the expression of B, receptor. Low-dose Ang-(1-7) infusion did not modify both the kinin B-1 and B-2 receptor expression compared with aCSF treatment group after focal cerebral ischemia-reperfusion at each time point. The finding might indicate complex interactions between Ang-(1-7) and kallikrein-kinin system in the CNS after focal cerebral ischemia-reperfusion in rats. (C) 2008 Elsevier B.V. All rights reserved.