Effects of Angiotensin II on Expression of the Gap Junction Channel Protein Connexin 43 in Neonatal Rat Ventricular Myocytes

Objectives To study the effects of angiotensin II, as a mediator of cardiac hypertrophy, on expression of connexin 43 (Cx43) in cultured neonatal rat ventricular myocytes and correlation of expression of Cx43 and cardiomyocyte hypertrophy. Methods Cardiomyocytes were isolated from newborn SD rats. Angiotensin II was added into the media to induce myocyte hypertrophy. Cultures were exposed to 10～6 mol/L angiotensin II for 72 h, Cx43 expression was characterized by RT-PCR and Immunofluorescence methods. Results Immunofluorescence analysis revealed decreased Cx43 immunoreactivity in cells treated for 72 h with angiotensin II. RT-PCR analysis demonstrated there was an obvious decrease of Cx43 mRNA level in cells exposed to angiotensin II for 72 h. The changes of expression of connexin 43 were related to its entrance into S phase of the cell cycle. Cultured neonatal rat cardiomyocytes were exposed for 72 h to increase concentrations of angiotensin II (1.0×10-9～1.0×10-6mol/L), resulting in significantly decreased Cx43 expression. Conclusions Angiotensin II leads to a concentration-dependent decrease in Cx43 protein in cultured neonatal rat ventricular myocytes by decreasing Cx43 mRNA synthesis. Signal transduction pathways activated by angiotensin II under pathophysiologic conditions of cardiac hypertrophy could initiate remodeling of gap junctions.