Effect of ß3-adrenergic receptor on atrial L-type Ca(2+) current in rats with chronic heart failure.

ABSTRACT

OBJECTIVES: To investigate the effect of selective ß3-adrenoreceptor agonist BRL-37344 on L-type Ca(2+) current (Ica,L) and mRNA expression of L-type Ca(2+) 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 (0.4nmol/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, P<0.01) or CHF control (4.0 ± 0.2mm, P<0.05) group. The LA ejection fraction in the BRL group (36.2 ± 4.2%) was lower than in the normal control (58.0 ± 3.1%, P<0.01) or CHF control group (42.3 ± 4.8%, P<0.05). There was no difference in Ica,L density between the BRL group and CHF control group (8.3 ± 1.7 vs. 8.2 ± 2.6 pA/pF, P>0.05), which was higher than in the normal control group (6.0 ± 1.8 pA/pF, P<0.01). 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, P>0.05), which was also higher than in the normal control group (0.137 ± 0.013, P<0.01). CONCLUSION: ß3-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 Ca(2+) channel α2δ-2 (Cacna2d2) subunit in the LA myocytes.