Abstract:
Objective To investigate the effect of intervention of serotonin 2Breceptor antagonist(SB215505)in vivo on cardiac function in pressure-overloaded rats. Methods Thirty-four adult male SD rats,weighing 200-230 g,were randomly divided into sham-operated group(n=14)and abdominal aorta coarctation(AAC)group(n=20).At the 9th week after the operation,rats in the sham-operated group were randomly divided into sham-operated8-week group and sham-operated 12-week group(n=7in each group),and rats in the AAC group were randomly divided into SB215505group(intraperitoneal injection of SB215505 with the dose of 1mg/(kg·d),which dissolved in DMSO at the concentration of 2mg/mL,and 1rat died during the injection;n=5,ACC 8-week group(n=7)and AAC12-week group(n=7). Sham-operated 8-week group and ACC 8-week group were killed immediately,and heart and blood samples were taken. Sham-operated 12-week group and ACC 12-week group received intraperitoneal injection of an equal volume of DMSO solution for 4weeks,and then were killed and the samples of heart and blood were taken. Left ventricular mass index(LVMI),left ventricular transdiameter of cardiomyocyte(LVTDM),cardiomyocytes surface area(CSA)and levels of BNP in the plasma were determined in each group. In the sham-operated 12-week group,ACC 12-week group and SB215505 group,left ventricular function was estimated by echocardiogram and the expression levels of transient receptor potential channel subtribe C type 3(TRPC3)protein were determined by Western blot and immunohistochemical method.Results Compared with the sham-operated 8-week group,LVMI,LVTDM,CSA and levels of BNP in the plasma were significantly increased in the AAC8-week group(all P<0.05). Compared with the sham-operated 12-week group,LVMI,LVTDM,CSA,levels of BNP in the plasma,left ventricular end systolic diameter(LVESD)and the expression levels of TRPC3 protein were significantly increased,while left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were decreased in the AAC12-week group(all P <0.05). Compared with the AAC12-week group,LVMI(1.95±0.13)vs(2.39±0.35)mg/g,LVTDM (17.70±2.48)vs(23.74±2.96)μm,CSA (279.1±74.2)vs(442.4±132.7)μm2,levels of BNP in the plasma (108.5±19.7)vs(583.5±82.4)ng/L,LVESD(4.15±0.95)vs(4.81±0.05)mmand expression levels of TRPC3protein(0.65±0.02 vs 0.92±0.04)were significantly decreased,while LVEF(0.77±0.01 vs 0.69±0.03)and LVFS(0.40±0.01 vs 0.34±0.02)were obviously increased in the SB215505group(all P<0.05). Conclusion SB215505 could partially inhibit ventricular remodeling and improve cardiac function in pressure-overloaded rats,which may attribute to the down-regulation of TRPC3 protein expression.