Reciprocal changes in active and inactive renin after converting enzyme inhibition in normal man.
Since one mechanism by which converting enzyme inhibition (CEI) increases renin is removal of angiotensin II negative feedback on the juxtaglomerular cell, we studied the time course of changes in active and inactive renin after CEI. After equilibration on a 25 meq/day sodium diet, captopril was given as a single 50-mg oral dose (acute phase), and then was administered as 50 mg every 6 h for 3 days to seven normal volunteers (chronic phase). In the acute phase, supine blood pressure fell 12 +/- 2 mm Hg (P less than 0.02). Active renin acutely increased 12.5 +/- 0.9 times the baseline value, peaking at 3-4 h. Inactive renin, measured by acid activation of trypsin activation, decreased in all subjects to 10% or less of control from 2 to as long as 6 h post-CEI and then returned to baseline levels by 8 h (P less than 0.01). With chronic CEI, active renin was elevated to 10.8 +/- 2.4 times the baseline level, and after 48 h inactive renin levels rose to 4.0 +/- 0.6 times the baseline (P less than 0.02). To determine whether the acute changes in inactive and active renin occurred because of captopril's effect on renin in the circulation or kidney, a single dose of captopril was administered to three subjects with mild to moderate renal insufficiency and hyporeninemic hypoaldosteronism. In contrast to normal subjects, these patients had no change in active and inactive renin levels when given captopril, suggesting that changes observed in the normals were renal mediated rather than a plasma phenomenon. We conclude that CEI 1) acutely increases active renin while reciprocally reducing the inactive form, and 2) chronically increases both active and inactive renin. These studies support the hypothesis that inactive renin may be a precursor of circulating active renin.
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril / Q000008:administration & dosage; D004789:Enzyme Activation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives*; D012083:Renin / Q000097:blood*; D014357:Trypsin
D000806:Angiotensin-Converting Enzyme Inhibitors; D000450:Aldosterone; D011392:Proline; D002216:Captopril; D014357:Trypsin; D012083:Renin