Downregulation of the β1 adrenergic receptor in the myocardium results in insensitivity to metoprolol and reduces blood pressure in spontaneously hypertensive rats

The β1adrenergic receptor (AR) is the primary βAR subtype in the heart and is the target of metoprolol (Met), which is commonly used to treat angina and hypertension. Previous studies have revealed a positive correlation between the methylation levels of the adrenoreceptor β1 gene (Adrb1) promoter in the myocardium with the antihypertensive activity of Met in spontaneously hypertensive rats (SHR), which affects β1AR expression in H9C2 cells. The aim of the present study was to investigate the effects of myocardial β1AR downregulation using shorthairpin RNA (shRNA) against Adrb1 on the antihypertensive activity of Met in SHR. Recombinant adenoassociated virus type 9 (rAAV9) vectors carrying Adrb1 shRNA (rAAV9Adrb1) or a negative control sequence (rAAV9NC) were generated and used to infect rat hearts via the pericardial cavity. The results of reverse transcriptionquantitative polymerase chain reaction, immunohistochemistry and western blotting analyses demonstrated that cardiac β1AR expression in the rAAV9Adrb1 group was significantly downregulated when compared with the rAAV9NC group (P<0.001, P<0.001 and P=0.032, respectively). In addition, a greater reduction in systolic blood pressure (SBP) was observed in the rAAV9NC group compared with the rAAV9Adrb1 group following Met treatment (P=0.035). Furthermore, downregulation of myocardial β1AR was associated with a significant decrease in SBP (P<0.001). In conclusion, these data suggest that suppression of β1AR expression in the myocardium reduces SBP and sensitivity to Met in SHR.