EFFICACY OF INTRARENAL ACE-INHIBITION ESTIMATED FROM THE RENAL RESPONSE TO ANGIOTENSIN-I AND ANGIOTENSIN-II IN HUMANS

Recent studies on the nature of the renin-angiotensin system (RAS) in animals have led to the concept that systemic and intrarenal RAS can b e influenced to different degrees by angiotensin converting enzyme (AC E) inhibitors. Assessment of efficacy of intrarenal ACE inhibition by ACE inhibitors in humans is necessarily indirect and has not been repo rted. We therefore monitored the renal response to acute angiotensin ( Ang) I infusion in volunteers taking 20 mg enalapril twice daily, and related the responses to the obtained increments in plasma Ang II leve ls. Ang I infusion rates of 4, 8, 16, and 32 pmol/kg/min caused gradua l increments in plasma Ang I (maximal change from 26 +/- 18 to 578 +/- 120 pmol/liter, P < 0.05) and, despite treatment with enalapril, also of Ang II (from 3 +/- 1 to 29 +/- 5 pmol/liter, P < 0.05). This was a ssociated with large reductions in renal plasma flow (para-aminohippur ate clearance), filtration fraction, maximal urine flow, sodium excret ion, lithium and uric acid clearance, and increments in mean arterial pressure and plasma aldosterone (P < 0.05 for each variable). Strong c orrelations existed between the changes in either variable and the inc rement in plasma Ang II. Infusions of Ang II at 1 and 4 pmol/kg/min in the same subjects caused comparable increments in plasma Ang II and h ad similar physiological effects as found during the Ang I infusion. A nalysis of covariance of the changes in plasma Ang II and each of the measured variables revealed no differences between Ang I and Ang II in fusions. Since Ang I had no functional effects in the kidney independe nt of the increments in plasma Ang II, additional intrarenal Ang I to Ang II conversion in the present experimental setting is unlikely. Thi s protocol provides an indirect method to assess efficacy of intrarena l ACE inhibition in humans.