Angiotensin II induced myocardial hypertrophy in neonatal rats could be attenuated by activated κ-opioid receptor via modulating the calcineurin signal pathways / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effect of κ-opioid receptor (κ-OR) stimulation on Angiotensin II (Ang II)-induced cardiomyocyte hypertrophy in vitro cultured myocardial cells from neonatal rats and on calcineurin (CaN) signal pathways.</p><p><b>METHODS</b>Cultured myocardial cells of neonatal rats were divided into control group, CSA (1 µmol/L) group, Ang II (1 µmol/L) group, Ang II (1 µmol/L) + U50488H (1 µmol/L) group, Ang II (1 µmol/L) + CSA (1 µmol/L) group, Ang II (1 µmol/L) + Rp-cAMPS (1 µmol/L) group, Ang II (1 µmol/L) + CSA (1 µmol/L) + U50488H (1 µmol/L) group and Ang II (1 µmol/L) + PTX5 mg/L + U50488H (1 µmol/L) group. The hypertrophic myocytes were induced by Ang II 1µmol/L before κ-OR agonist U50488H 1 µmol/L was administered. The antihypertrophic effect of κ-OR stimulation was observed in the presence of ciclosporine A (CsA) 1 µmol/L, cAMP triethyl-ammonium salt (Rp-cAMPS) 1 µmol/L, and pertussistoxin ( PTX) 5 mg/L. The total protein content was assayed by the method of Lowry. The [Ca²⁺]i was measured by confocal microscope using Fluo-3/AM as flouresecent indicator. The relative expression of CaN was determined by Western blot.</p><p><b>RESULTS</b>(1) The total protein content of Ang II group was significantly higher than that in control group (P<0.01), which could be equally reduced by cotreatment with U50488H, CSA and Rp-cAMPS (P<0.01). Total protein content of the Ang II + PTX + U50488H group and the Ang II group was similar. (2) The [Ca²⁺]i was significantly higher in Ang II group of neonatal rat cardiomyocytes than that in control group (P<0.01), which could be reduced by cotreatment with U50488H, CSA and Rp-cAMPS (P<0.01). [Ca(2+)]i was similar between the Ang II + PTX + U50488H group and the Ang II group. (3) The expression of CaN was significantly higher in Ang II group than that in control group (P<0.01), which could be significantly reduced by cotreatment with U50488H, CSA and Rp-cAMPS (P<0.01). CaN was similar between the Ang II + PTX + U50488H group and the Ang II group.</p><p><b>CONCLUSION</b>κ-opioid receptor activation could attenuate Ang II induced cardiomyocytes hypertrophy via reducing [Ca²⁺]i and downreglating CaN.</p>