Effect of β3-adrenergic receptor on atrial L-type Ca(2+) current in rats with chronic heart failure

Heart Lung Circ. 2014 Apr;23(4):369-77. doi: 10.1016/j.hlc.2013.08.008. Epub 2013 Sep 1.

Abstract

Objectives: To investigate the effect of selective β3-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: 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 Ca(2+) channel α2δ-2 (Cacna2d2) subunit in the LA myocytes.

Keywords: Atrium; Heart failure; Rat; Ventricular function; β(3)-Adrenoreceptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Calcium Channels, L-Type / metabolism*
  • Chronic Disease
  • Ethanolamines / pharmacology
  • Heart Atria / metabolism
  • Heart Atria / physiopathology
  • Heart Failure / metabolism*
  • Heart Failure / pathology
  • Heart Failure / physiopathology
  • Male
  • Myocardium / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, beta-3 / metabolism*

Substances

  • Adrenergic beta-Agonists
  • Cacna2d2 protein, rat
  • Calcium Channels
  • Calcium Channels, L-Type
  • Ethanolamines
  • Receptors, Adrenergic, beta-3
  • BRL 37344
  • Calcium