Effects of different doses of aliskiren on the expression of renin angiotensin system in a canine model with rapid atrial pacing

Abstract

Objective To investigate effects of the different doses of aliskiren on levels of angiotensin converting enzyme (ACE) and angiotensin Ⅱ (Ang Ⅱ) and on the mRNA expressions of ACE2 and Ang II type 1 receptor (AT1R) in atrial tissues after rapid atrial pacing of a canine model. Methods A total of 24 healthy adult dogs were selected and assigned into sham, control(atrial pacing), paced dog + aliskiren (10 mg kg-1 d-1, low-dose), paced dog + aliskiren (20 mg kg-1 d-1, high-dose) groups (n=6, for each group). Rapid atrial pacing at 500 beats per minute was maintained for 2 weeks, but dogs in sham group were instrumented without pacing. The control group received pacemaker implantation and atrial pacing without drug intervention. A low- and high-dose of Aliskiren (10 mg kg-1 d-1 or 20 mg kg-1 d-1) were given orally before atrial pacing for 3 days. Enzyme linked immunosorbent assay (ELISA) were applied to assess the levels of ACE and Ang II in serum and atrial tissue, and reverse transcription-polymerase chain reaction (RT-PCR) were applied to assess the mRNA expressions of ACE2 and AT1R in atrial tissues of the different groups. Results ACE and AngⅡ levels in atrial tissue in sham group were (1.18±0.24) ng/mg, and (10.61±2.24) pg/mg, and increased to (2.38±0.50) ng/mg and (26.16±4.09) pg/mg after 2 weeks of rapid atrial pacing in sham group . ACE and AngⅡ levels in atrial tissue were (1.54±0.27) ng/mg and (1.45±0.31) ng/mg, (19.41±2.05) pg/mg and (14.26±1.99) pg/mg in lose- and high-dose aliskiren-treated groups respectively. The levels of ACE and AngⅡ in atrial tissue were reduced in aliskiren intervention group, and AngⅡ level declined in a dose dependent manner (F=17.32 and 39.78, all P<0.01). Conclusions Aliskiren can suppress the atrial fibrillation vulnerability by decreasing ACE and AngⅡ levels and AT1R mRNA expression and increasing ACE2 mRNA expression. Aliskiren reduces AngⅡ levels and AT1R mRNA expression in a dose dependent manner. Key words: Atrial Fibrillation; Aliskiren; Renin-angiotensin system