ACUTE BUT NOT CHRONIC ANGIOTENSIN-CONVERTING ENZYME-INHIBITION INDUCES ENZYME-SYNTHESIS IN THE GLOMERULUS OF THE SPONTANEOUSLY HYPERTENSIVERAT

1. Treatment with angiotensin-converting enzyme (ACE) inhibitors slows the rate of progression of nephropathy in the spontaneously hypertens ive rat (SHR) with streptozotocin-induced diabetes, Paradoxically, how ever, chronic ACE inhibitor therapy has been reported to be associated with induction of ACE in the plasma, We sought to determine whether i nduction also occurred in the glomerulus. 2. Seven days after inductio n of diabetes rats were randomized to receive perindopril (4mg/kg per day) in the drinking water or water alone, Blood glucoses were maintai ned 6-10 mmol/L by daily ultralente insulin. Rats were killed after 1 and 12 weeks of ACE inhibitor therapy and the kidneys were harvested, Angiotensin-converting enzyme activity was determined in isolated glom eruli before and after removal of perindopril and reconstitution with zinc sulphate. 3. After 1 week of ACE inhibitor therapy, glomerular AC E was significantly greater after removal of perindopril than either b efore its removal (P < 0.025) or in the untreated controls (P < 0.025) , After 12 weeks of therapy, ACE activity was significantly lower in t he perindopril-treated group than in the untreated controls (P<0,025), There was no increase in ACE activity following removal of perindopri l. 4. These studies suggest that short-term ACE inhibition is associat ed with induction of ACE in the glomerulus, However, there was no incr ease in ACE activity after removal of perindopril, suggesting that ind uction of synthesis of this enzyme in the glomerulus does not occur du ring chronic ACE inhibition.