Angiotensin II Receptor Antagonist Blocks the Expression of Connexin43 Induced by Cyclical Mechanical Stretch in Cultured Neonatal Rat Cardiac Myocytes

Mechanical forces have profound effects on cardiomyocytes. To test whether angiotensin II is a potential mediator of stretch-induced effects on gap junctions, we used the angiotensin II (AT1) receptor antagonist, losartan, to investigate the cyclical stretch-induced expression of connexin43 (Cx43), the major cardiac muscle gap junction channel protein. Cultured neonatal rat cardiomyocytes grown on a flexible membrane base were stretched by vacuum to 20% of maximum elongation, at 60 cycles/min. The levels of Cx43 protein began to increase as early as 2 h after stretch was applied, reached a maximum of six-fold over the control by 24 h and remained at this level another 24 h (i.e. up to 48 h after stretch was applied). These increases of Cx43 protein at 24 h were largely (73%) and completely (100%) attenuated (P