Renin-angiotensin system and cell communication in the failing heart

The influence of heart failure on the process of cell communication was investigated in cell pairs isolated from the ventricle of cardiomyopathic hamsters (11 months old) and the results compared with age-matched normal hamsters. The gap junctional conductance (gj) was measured with two voltage-clamp amplifiers. The results showed two major populations of cell pairs with respect to gj values: one with very low values (0.8 to 2.5 nS) and the other with higher values (7 to 35 nS). In normal hamsters, the most frequent gi values were in the range of 40 to 100 nS. Angiotensin II (Ang II, 1 mu g/mL) caused cell uncoupling in myopathic myocytes with low gi but reduced gi by 53+/-6.6% (+/-SE) in cell pairs with higher gj values (7 to 35 nS). The effect of Ang II on gj of myopathic cell pairs was suppressed by losartan (10(-7) mol/L). In cardiomyopathic cell pairs with low gj (0.8 to 2.5 nS), enalapril (1 mu g/mL) caused an appreciable increase in gi (219+/-20.3%), whereas in cell pairs with higher gj (7 to 35 nS), the gj increment was smaller (80+/-10.8%) but still larger than that seen in controls (33+/-5.4%). Intracellular dialysis of Ang I (10(-8) mol/L) abolished cell communication in myopathic cell pairs with low gi (0.8 to 2.5 nS) and reduced gj by 66+/-1.7% in the other pairs (7 to 35 nS). The effect of Ang I on gj was greatly reduced by enalaprilat (10(-9) mol/L) added to the cytosol. Dialysis of Ang II (10(-8) mol/L) into the myopathic cell reduced gj by 48+/-4.2%, an effect abolished by losartan (10(-8) mol/L). The results indicate that the decline in gi seen in the ventricle of cardiomyopathic hamsters is in part due to activation of the cardiac renin-angiotensin system.