The Study Of Changes Of AT₁Receptor And NADPH Oxidase System Expression And The Intervention Effect Of Valsartan In Rats After Myocardial Infarction

Objective To investigate the changes of Angiotensin II type1receptor (AT] receptor) and NADPH oxidase system expression and the intervention effect of valsartan in rats after myocardial infarction(MI).Methods Healthy male Sprague Dawley rats weighing230～260g were used and anesthetized by intraperitoneal injection of3%pentobarbital(2ml/kg). After endotracheal intubation, thoracotomy was performed, MI rats were made by ligation of anterior descending coronary artery, the Sham group underwent the same procedure without coronary artery ligation. MI rats were assigned randomly to intragastrically receive valsartan (10mg/kg/d), named MI intervention group or isovolumetric saline, named MI group on the second day after procedure. A total of25rats survived in the sixth week,10rats were in Sham group,6rats in MI group and9rats in MI intervention group. The rats were killed after anesthesia, left ventricle was separated and weighed. Non-infarcted left ventricular myocardium was taken and frozed in liquid nitrogen. The expression level of AT1receptor mRNA and gp91phox mRNA were detected with RT-qPCR, gp91phox protein level was measured with Western-Blot, and the concentration of superoxide anion(O2) and the activity of NADPH oxidase were measured by WST-1method,Results1.The expression level of AT1receptor mRNA and gp91phox mRNA in MI group were (3.70±1.45) times and (4.57±1.84) times than Sham group, there were significant difference between the two groups (P<0.01). The expression level of ATi receptor mRNA and gp91phox mRNA in MI group were (3.08±1.34) times and (2.87±1.75) times than MI intervention group, there were significant difference(P<0.01). In MI intervention group, the expression level of AT1receptor mRNA was (1.20±1.06) times than Sham group, with no significance between them(P>0.05), the expression level of gp91phox mRNA was (1.59±1.08) times than Sham group, there was statistical difference(P<0.05).2. The Gamma ratio of gp91phox protein to GAPHD were (0.98±0.26) and (0.37± 0.09) respectively in MI group and Sham group, there was significant difference between the two groups (P<0.01), In MI intervention group, the Gamma ratio of gp91phox protein to GAPHD was (0.58±0.13), significantly lower than MI group(P<0.01), but higher than Sham group(P<0.05).3. The concentration of O2-and the activity of NADPH oxidase were (21264.83±1354.36)RLU/mg and (4.65±0.54)RLU/mg respectively in MI group, significantly increased compared with Sham group [(7812.75±1078.71)RLU/mg and (2.69±0.18)RLU/mg, respectively](P<0.01). The concentration of O2-and the activity of NADPH oxidase in MI intervention group were (9027.93±1236.47)RLU/mg and (2.91±0.23)RLU/mg respectively, significantly lower than MI group(P<0.01), but higher than Sham group(P<0.05).4. The expression level of gp91phox mRNA and AT1receptor mRNA positively correlated(R=0.708, P<0.01). The concentration of O2-also positively correlated with the expression level of gp91phox mRNA(R=0.704, P<0.01) and the activity of NADPH oxidase (R=0.831, P<0.01).5. Left ventricular mass index (LVMI)was (7.46±0.54) mg/g in MI group, Sham group was (5.04±0.71) mg/g, there was significant difference between the two groups(P<0.01). MI intervention group was (5.74±0.66) mg/g, significantly reduced than MI group(P<0.01), but without significance compared with Sham group (P>0.05).Conclusion1. The expression of AT1receptor mRNA, gp91phox mRNA and protein, the activity of NADPH oxidase and the concetration of O2-in non-infarcted left ventricular myocardium, and LVMI in MI group increased significantly compared with Sham group, this suggests NADPH oxidase system and RAS system are activated, left ventricular remoding occurs after myocardial infarction.2. The expression of AT1receptor mRNA, gp91phoxmRNA and protein, the activity of NADPH oxidase and the concetration of O2-in non-infarcted left ventricular myocardium, LVMI in MI intervention group decreased significantly compared with MI group, this indicates valsartan reduces the activity and expression of NADPH oxidase to decrease the producion of O2-by blocking AT1receptor, and prevents left ventricular remodeling.