Renin increments the inward calcium current in the failing heart

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Abstract
Background Evidence is available that activation of the renin–angiotensin system is involved in cardiac remodeling. It is unknown whether renin can change the inward calcium current (ICa) in the failing heart. This problem was investigated in the present study. Methods Cardiomyocytes were isolated from the ventricle of 4-month-old cardiomyopathic hamsters and measurements of the L-type ICa were performed using the patch-clamp technique in a whole-cell configuration. Results Extracellular renin (128 pmol Ang I/ml per min) plus angiotensinogen (110 pmol angiotensin I generated by renin to exhaustion) incremented the peak ICa density significantly, an effect suppressed by enalapril maleate (10−8 mol/l) or by losartan (10−7 mol/l) added to the bath, indicating that the effect of renin plus angiotensinogen was related to the formation of angiotensin I and its conversion to angiotensin II at the surface cell membrane. Renin internalization seems to increment the ICa because intracellular dialysis of renin (128 pmol Ang I/ml per min) plus angiotensinogen (110 pmol angiotensin I generated by renin to exhaustion) also increased the peak ICa density significantly, an effect suppressed by intracellular losartan (10−8 mol/l) but not by extracellular losartan (10−7 mol/l). Conclusions Extracellular renin plus angiotensinogen increases the ICa in isolated myocytes from the failing heart of cardiomyopathic hamsters through the formation of angiotensin II and the activation of angiotensin type 1 receptors at the surface cell membrane. A similar increment of ICa was found with intracellular administration of renin plus angiotensinogen. This finding might indicate that renin internalization is involved in control of inward calcium current in the failing heart.