Influence of angiotensin-(1-7) on inducible nitric oxide synthase expression after focal cerebral ischemia-reperfusion in rats
10.3760/cma.j.issn.1006-7876.2011.02.013
- VernacularTitle:血管紧张素-(1-7)对大鼠局灶性脑缺血再灌注损伤后诱导型一氧化氮合酶表达的影响
- Author:
Jie LU
;
Yingdong ZHANG
;
Jingping SHI
- Publication Type:Journal Article
- Keywords:
Brain ischemia;
Reperfusion injury;
Angiotensins;
Nitric oxide synthase;
Rats
- From:
Chinese Journal of Neurology
2011;44(2):128-131
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate influence of Ang-(1-7) on the inducible nitric oxide synthase (iNOS) activity and gene expression following focal cerebral ischemia/reperfusion in rats. Methods Cerebral ischemia/reperfusion injury was induced by intraluminal thread occlusion of middle cerebral artery in the adult male Sprague-Dawley (SD) rats. Ang-(1-7) or artificial cerebrospinal fluid (aCSF) was continuous administrated by implanted Alzet osmotic minipumps into lateral cerebral ventricle after reperfusion. Experimental animals were divided into sham-operated group ( sham operation + aCSF), aCSF treatment group(MCAO+aCSF)and ang-(1-7)treatment groups(MCAO+Ang-(1-7))at low(1 pmol·0.5 μl-1·h-1),medium (100 pmol·0.5 μl-1·h-1)or hith(10 nmol·0.5 μl-1·h-1)dose levels.The activity of iNOS in ischemic tissues were measured by iNOS detection kits. Reverse transcription( RT)-PCR was used to determine messenger RNA (mRNA) of the iNOS in ischemic tissues. Results The cerebral ischemic lesion resulted in a significant increase of iNOS expression compared with sham operation group. The high-dose Ang-(1-7) markedly enhanced (iNOS) activity ( 160. 83 vs 116. 75 U/mg, F = 19. 22,P<0.01; 151.87 vs 113.07 U/mg, F=63.52,P<0. 01) and gene expression(0.43 vs 0.38, F=21.83,P < 0. 01; 0. 40 vs 0. 35, F = 19.49, P < 0. 01 ) compared with aCSF treatment group at 24 hours and 48hours after reperfusion, whereas medium and low-dose Ang-( 1-7 ) didn't stimulate iNOS activation.Conclusions The obtained results suggest that high-dose Ang-(1-7) upregulate iNOS expression following ischemic stroke.Moreover,overdose Ang-(1-7)(10 nmol·0.5 μl-1·h-1)may have Ang Ⅱ-like effects in iNOS expression increase.