Central administration of angiotensin-(1-7) stimulates nitric oxide release and upregulates the endothelial nitric oxide synthase expression following focal cerebral ischemia/reperfusion in rats.
Angiotensin-(1-7) [Ang-(1-7)] is an endogenous peptide of the renin-angiotensin system with several beneficial effects that are often opposite to those attributed to angiotensin II (Ang II). Since there are no data available so far on the role of Ang-(1-7) after cerebral ischemia/reperfusion, in this paper, we investigated the central administration of Ang-(1-7) modulates in vivo the nitric oxide(NO) release and the endothelial NO synthase (eNOS) expression following focal cerebral ischemia/reperfusion in rats. Cerebral ischemia-reperfusion injury was induced by intraluminal thread occlusion of middle cerebral artery in the adult male rats. The levels of NO in ischemic tissues were measured by NO detection kits. Reverse transcription (RT)-PCR and western blot were used to determine messenger RNA (mRNA) and protein levels of the eNOS in ischemic tissues. The cerebral ischemic lesion resulted in a significant increase of NO release at 3 and 6h compared with sham operation group in our model after reperfusion, whereas both medium and high doses Ang-(1-7) markedly enhanced NO levels at 3-24h, and 3-72h after reperfusion, respectively. In addition, NO release increased was significantly induced by high-dose Ang-(1-7) compared with medium-dose Ang-(1-7) at 24-72 h after reperfusion. Medium and high-dose Ang-(1-7) significantly stimulated eNOS activation when compared with artificial cerebrospinal fluid (aCSF) treatment group at 3, 6, 12, 24, and 48h after reperfusion, however, no significant changes in eNOS expression were found between medium and high-dose Ang-(1-7) at different times after the ischemic insult. These findings indicate that medium and high-dose Ang-(1-7) stimulate NO release and upregulate eNOS expression in ischemic tissues following focal cerebral ischemia/reperfusion in rats.
Zhang
Yingdong
Y
Department of Neurology, Nanjing Brain Hospital, Nanjing Medical University, No. 264 Guangzhou Road, Nanjing 210029, PR China. zhangyingdong@yahoo.com.cn
Lu
Jie
J
Shi
Jingping
J
Lin
Xingjian
X
Dong
Jingde
J
Zhang
Shugang
S
Liu
Yan
Y
Tong
Qiang
Q
D000803:Angiotensin I / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D015854:Up-Regulation
D010446:Peptide Fragments; D009569:Nitric Oxide; D000803:Angiotensin I; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C118790:angiotensin I (1-7)