Effect of β3-Adrenergic Receptor on Atrial L-type Ca2+ Current in Rats with Chronic Heart Failure

摘要

Objectives: To investigate the effect of selective β3-adrenoreceptor agonist BRL-37344 on L-type Ca2+ current (Ica,L) and mRNA expression of L-type Ca2+ channel α2δ-2 (Cacna2d2) in rats with chronic heart failure (CHF). Methods: Twenty-four male Wistar rats were divided into normal control (n= 6) and CHF group (n= 18), which were further divided into CHF control and BRL group (0.4. nmol/kg, IV, twice weekly for four weeks). Echocardiography was performed to assess the structure and function of the left atrium (LA). Results: The LA in the BRL group (4.4±0.2mm) was larger than in the normal control (3.5±0.3mm, P0.01) or CHF control (4.0±0.2mm, P0.05) group. The LA ejection fraction in the BRL group (36.2±4.2%) was lower than in the normal control (58.0±3.1%, P0.01) or CHF control group (42.3±4.8%, P0.05). There was no difference in Ica,L density between the BRL group and CHF control group (8.3±1.7 vs. 8.2±2.6pA/pF, P0.05), which was higher than in the normal control group (6.0±1.8pA/pF, P0.01). There was no difference in the mRNA expression of α2δ-2 (Cacna2d2) between the BRL group and CHF control group (0.264±0.005 vs. 0.243±0.017, P0.05), which was also higher than in the normal control group (0.137±0.013, P0.01). Conclusion: β3-Adrenoreceptor stimulation with BRL-37344 was associated with an increase in LA diameter and a decrease in LA function in chronic heart failure. These structural and function changes were not related to Ica,L or L-type Ca2+ channel α2δ-2 (Cacna2d2) subunit in the LA myocytes.