Effect Of β₃-adrenergic Receptor Upregulation In Left Ventricular Myocardium On Left Ventricular Function In Post-infarcted Rats

Background and objective: β₃-adrenergic receptor (β₃AR) in left ventricular myocardium is upregulated when heart failure occurs. Up to now, there has been no agreement about that the inotropic effect induced by β₃AR is negative (NIE) or positive (PIE). We speculate that heart failure happens when β₃AR is not enough compensatorily upregulated to surpass the heart failure-inducing factors; By early intervention treatment with β₃AR-related agents before the occurrence of heart failure, the resultant further upregulation of β₃AR might be cardioprotectant retarding or preventing heart failure. Moreover, β₃AR stimulation might be involved in angiogenesis. Our present study was to investigate the role of β₃AR in the development of heart failure in post-infarcted rats by detecting β₃AR expression and capillary proliferation in non-infarcted myocardium and by measuring left ventricular function.Materials and methods: 120 Male Sprague Dawley rats weighing 210～250g were randomly assigned into 5 groups: normal rats (group NM), sham-operated rats (group SM), infarcted rats (group IF), infarcted rats injected with vehicle (group TV) and infarcted rats treated with BRL37344 (group IB). Myocardial infarction models were produced by coronary artery ligation. Sham-operated rats were treated similarly except that the suture was not tied around the coronary artery. The final sample sizes were 10, 7, 9, 9 and 10 respectively in group NM, SM, IF, IV and IB. Hemodynamic measurements were performed by the right femoral artery cannulation and by the left ventricle cannulation via right common carotid artery. By PC connected to the pressure transducer, hemodynamic parameters were recorded including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MBP), left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and maximum rise or fall rate of left ventricular pressure (+dp/dtmax or -dp/dtmax). After the rats were sacrificed by decapitation, the left and right ventricles were weighed, parts of the left ventricle were paraffin-embedded for measuring infarct size, HE staining, and β₃AR immunohistochemical staining. The rest parts were stored at -70℃for detecting β₃AR by western blotting. Statistical analysis: Data were expressed as X ± SD.The ratio of left ventricular weight to body weight (LVBW) and ±dp/dtmax were analyzed bymultivariate ANOCOVA, the other data were analyzed by two-way ANOVA. Statisticalsignificance was established at P<0.05. All statistical analyses were performed using SAS8.2software.Results: Western blotting results showed IB had the greatest β₃AR protein level (P<0.05,...