Experiment Research On Role Of H₂receptor Blocker In Aorta Arch Constriction Induced Cardiac Hypertrophy In Mice

AIM:1) To compare two cardiac hypertrophy mouse models established respectivelyby transverse aortic constriction or by isoprenaline hydrochloride.2) After the operation of TAC, observe, analysis and compare the effect of β1receptor blocker, Atenolol, in the administration group with the controlgroup and the model group.3) After the operation of TAC, observe, analysis and compare the effect of H2receptor blocker, Famotidine, in the administration group with the controlgroup and the model group.METHODS:1) Establish cardiac hypertrophy mouse models respectively by TAC or by theadministration of IPH.2) Take the administration of Atenolol and/or Famotidine. 3) Take the Echocardiographic assessments, measure the cardiac myocytesshape and left ventricular mass to body weight ratio.4) Execute the PCR amplification of the hypertrophic related genes and thenanalyze them by agarose gel electrophoresis.RESULTS:1) Both isoprenaline hydrochloride injection and aorta arch constrictionsuccessfully established experimental models of cardiac hypertrophy.Compared with those in Normal group, LVIDs increased by36.06%, EF andFS decreased by24.88%and29.22%respectively (P<0.05), and the cardiacmyocytes shape increased by24.80%(P<0.001) in group IPH. LVM/BWincreased obviously (P<0.001), LVIDd and LVIDs increased respectively by27.42%and54.81%, LVEF and FS decreased by37.40%and42.17%respectively (P<0.01), and the cardiac myocytes shape increased by48.39%(P<0.001) in group TAC. LVM/BW and the cardiac myocytes shape ingroup TAC obviously increased compared with those in group IPH (P<0.01and P<0.001, respectively).2) After4weeks’ administration of Atenolol, compared with those in TACgroup, the LVIDd decreased24.9%、17.7%and18.2%respectively inNormal group, Sham group and Atenolol group, the LVIDs decreased32.9%,34.1%and26.3；while the EF increased65.6%,75.8%and49.5%, theFS increased79.7%,100.0%and62.6%respectively （P<0.05）.TheLVM/BW and the cardiac myocytes shape showed a decrease in Atenololgroup compared with the TAC group（P<0.01）.The expression of ANP,BNPand α-MHC of Atenolol group were lower than that in TAC group（P<0.05）.3) After4weeks’ administration of Famotidine, compared with TAC group, theLVIDd and the LVIDs showed lower in group Dose1, Dose2, Dose3and group Famo+Aten, while the EF and FS were higher（P<0.05）.TheLVM/BW and cardiac myocytes shape of the other five groups were lowerand smaller than that of TAC group（P<0.05）. Compare the LVM/BW andcardiac myocytes shape among Atenolol group, Dose2group andFamo+Aten group, the Famo+Aten group were lower than the other two（P<0.05）. The expression of ANP,BNP and α-MHC of the other fivegroups were lower than that in TAC group（P<0.05）. In addition, there weresignificant differences of the expression of these genes between groupDose1and group Dose3（P<0.01）.CONCLUSION:1) Cardiac hypertrophy mouse model induced by aorta arch constriction maywell mimic the pressure overload-induced hypertrophy, and itspathophysiological development is more similar to the pressureoverload-induced hypertrophy. Model induced by aorta arch constriction isan ideal model of cardiac hypertrophy than IPH injection method.2) By blocking the β1receptor in the TAC model mice, there have inhibition ortreatment effect on the stress overload induced myocardial hypertrophy,demonstrating that this receptor does participate in the pathological processof myocardial hypertrophy.3) By blocking the H2receptor in the TAC model mice, there’s also a cardiacprotection effect, which suggesting that the histamine may involvedregulation of the pathological process of myocardial hypertrophy by its H2receptor, and may have a synergistic effect together with the β1receptor.