Influence of angiotensin-(1-7) on inducible nitric oxide synthase expression after focal cerebral ischemia-reperfusion in rats / 中华神经科杂志

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.