Effects of captopril and enalapril on sodium excretion and blood pressure in sodium-deficient dogs.

Inhibition of angiotensin I-converting enzyme (ACE) (kininase II) provides a powerful new method for evaluating the role of the renin-angiotensin-aldosterone and kallikrein-kinin systems in the control of aldosterone secretion, renal function, and arterial blood pressure. This study compares the effects of long-term administration of a sulfhydryl inhibitor, captopril, with a nonsulfhydryl inhibitor, enalapril (1-[N-[1-(ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-L-proline), in conscious sodium-deficient dogs. Plasma aldosterone concentration (PAC), plasma renin activity (PRA), urinary sodium excretion (UNaV), arterial pressure (AP), blood kinins (BK), urinary kinins (UK), and urinary kallikrein activity (UKA) were determined during long-term inhibition of ACE in sodium-deficient dogs. In response to captopril administration (20 mg/(kg . day], PAC decreased from 38.9 +/- 6.7 to 14.3 +/- 2.3 ng/dl, PRA increased from 3.58 +/- 0.53 to 13.7 +/- 1.6 ng/(ml . h), UNaV increased from 0.65 +/- 0.27 to 6.4 +/- 1.2 meq/day, AP decreased from 102 +/- 3 to 65 +/- 2 mm Hg, BK increased from 0.17 +/- 0.02 to 0.41 +/- 0.04 ng/ml, UK increased from 7.2 +/- 1.5 to 31.4 +/- 3.2 micrograms/day, and UKA decreased from 23.6 +/- 3.1 to 5.3 +/- 1.2 EU/day. Quantitatively similar changes in AP, UNaV, and PAC were observed in sodium-deficient dogs in response to long-term enalapril administration (4 mg/(kg X day]. In sodium-deficient dogs maintained on captopril or enalapril for several days, angiotensin II (AngII) infusion (3 ng/(kg X min] restored PAC, UNaV, and AP to levels observed in untreated sodium-deficient dogs. These data indicate that the long-term hypotensive and natriuretic actions of inhibitors of ACE are mediated by inhibition of AngII formation and that the renin-angiotensin system plays an essential role in regulating aldosterone secretion, renal function, and AP during sodium deficiency.