Renin increments the inward calcium current in the failing heart

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 (I-ca) 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 I-Ca 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 I-Ca 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 I-Ca 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 I-Ca 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.