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 cerebrospinal 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 microl/h), medium (100 pmol/0.5 microl/h) or high (10 nmol/0.5 microl/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(1) 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.
Department of Neurology, Nanjing Brain Hospital, Nanjing Medical University, No. 264 Guangzhou Road, Nanjing, 210029, PR China.
Jie
J
Lu
Yingdong
Y
Zhang
Jingping
J
Shi
D000704:Analysis of Variance; D000803:Angiotensin I / Q000008:administration & dosage*; D000818:Animals; D001920:Bradykinin / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018002:Receptors, Bradykinin / Q000235:genetics / Q000378:metabolism*; D015424:Reperfusion / Q000379:methods*
D010446:Peptide Fragments; D012333:RNA, Messenger; D018002:Receptors, Bradykinin; D000803:Angiotensin I; C118790:angiotensin I (1-7); D001920:Bradykinin