The Effect Of Pyr3Blockade On Pressure Overload-induced Left Ventricular Hypertrophy Of Rat

Background and objective Long-term hypertension induced leftventricular hypertrophy (LVH) will eventually development into heartfailure, cardiac arrhythmias, ischemia, and even sudden death, etc. Theprevention and reversion of LVH has become one of the main trends of thecardiovascular research in recent years. Seeking effective pharmacologicaltargets from the formation mechanism of LVH is a hot spot in recent year’sresearch. Transient receptor potential canonical (TRPC) channel isnonselective Ca2+channel located in the cell membrane, and TRPC3is oneimportant member of the TRPC family. In recent years, numerous studieshave shown that TRPC channel especially TRPC3channels could regulatethe process of cardiac hypertrophy by adjusting the Ca2+change andactivating calcineurin(CaN)/activated T cell nucleus factor (NFAT)signaling pathways. Here, left ventricular hypertrophy rats model inducedby pressure overload is established by abdominal aorta surgery (AAC),pyr3(baton rouge-1-(4-(2filling-trichloroacrylamide) phenyl)-5-(trifluoromethyl)1h-Pyrazole-4-carboxylate), the selective blocker of TRPC3, was used to interfere in rats in vivo. The purpose is to explore theeffect of pyr3blockade on LVH and TRPC3and CaN Aβ protein andmRNA expression level of pressure overload rats in vivo.Methods The pressure overload model was established by abdominalaorta coarctation (AAC).30male SD rats were randomly divided into fivegroups(n=6/each group): sham operation control group, operation controlgroup, sham operation with whole-stage dosing (dosed with pyr3from the6th day after operation to the6th weekend) group, operation withlater-stage dosing (dosed with pyr3from the5th week after operation to the6th weekend) group, operation with whole-stage dosing group. The bloodpressure of each group was observed before and after operation (2,4,6weekend). Left ventricular mass index (LVMI) and left ventricularcardiomyocytes transaction diameter (LVTDM) of each group wereexamined after6weeks. The mRNA expression of transient receptorpotential canonical3(TRPC3) channel and calcineurin Aβ (CaN Aβ) wasmeasured by RT-PCR. The protein expression of TRPC3and CaN Aβ wasdetected by immunohistochemistry and Western blot.Results In the2nd,4th,6th weekend after operated, the bloodpressure of the three operation groups are all significantly higher than thatin the two sham operation groups（P＜0.05), there is no significantdifference on the blood of each stage before and after operation both amongthe three operation groups and between the two sham operation groups. In comparison with the sham operation control group, the left ventricularhypertrophy related indexes (left ventricular mass index and left ventricularcardiomyocytes transaction diameter) and the proteins and mRNAexpression of TRPC3and CaNAβ in the operation control group issignificantly increased(P <0.05); The hypertrophy related indexes of thesham operation with whole-stage dosing group showed no obviousdifference from the sham operation control group, but an up-regulation ofthe protein and mRNA expression of the TRPC3and CaNAβ wereobserved (P＜0.05).Compared with the operation control group, thehypertrophy related indexes, mRNA and protein expression of TRPC3andCaN Aβ in the operation with whole-stage dosing group were significantlydecreased(P＜0.05); The hypertrophy related indexes, mRNA and proteinexpression of CaNAβ in the operation with later-stage dosing group werealso significantly lower than that in the operation control group (P <0.05),but the difference of mRNA and protein expression of TRPC3showed nosignificance between the operation control group and the operation withlater-stage dosing group.Conclusion Pressure overload-induced LVH will be partly preventedby treatment of pyr3in vivo as well as the expression up-regulation ofTRPC3and CaN Aβ in the heart of pressure overload rat will besuppressed.