Abstract

Previous studies of RAS inhibition in Syrian cardiomyopathic hamsters (SCH) using the renin inhibitor aliskiren (10 mg/kg/day) suggested that the kidney at variance with the heart, is resistant to renin inhibition. RAS inhibition induces compensatory increases in ACE activity in target tissues. Thus, we hypothesized that ACE in kidney homogenates, is relatively insensitive to treatment with aliskiren in contrast to those from heart and plasma. To test this hypothesis, ACE activity was determined in plasma, heart and kidney homogenates, from 6‐month‐old SCH treated over 5 months with aliskiren, valsartan (AT1receptor blocker), and these drugs in combination. Age‐matched golden hamsters were used as controls (CT). ACE activity was determined, using a fluorimetric assay. Compared to CT, basal ACE activity in SCH is higher in the kidney, heart and plasma by 12% (P<0.05), 93% (P<0.05) and 12% (P<0.05), respectively. Neither aliskiren nor valsartan changed ACE activity in the heart, kidney or plasma of SCH. The combination of these drugs however, increase ACE activity only in SCH hearts (30%, P<0.05). These results suggest that the differential ACE activity that occurs in the heart, kidney, and plasma of SCH after RAS suppression may explain the observed differences in organ protection in this animal model. The reason for these differential effects of aliskiren is unknown. Supported by MBRS‐RISE R25‐GM061838.

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