Interaction of angiotensin converting enzyme inhibition and atrial natriuretic factor

The interaction of angiotensin converting enzyme (ACE) inhibition and atrial natriuretic factor (ANF) was investigated in six supine, sodium-replete, normal volunteers who received captopril (10 mg i.v. bolus followed by 10 mg/hr constant infusion) or vehicle superimposed on background 3-hour, constant, low-dose (1.5 pmol/kg/min) infusions of human ANF (99-126). Plasma converting enzyme activity was significantly inhibited but this had no effect on endogenous plasma ANF concentrations. ANF infusions, with or without captopril, caused similar increases in plasma ANF concentrations, and calculated metabolic clearance rates for ANF were unchanged. Similarly, blood pressure, heart rate, renal blood flow, glomerular filtration rate, and renal electrolyte excretion, including ANF-induced natriuresis, were unaffected by captopril. The combination of ANF plus captopril produced a significant increase in plasma aldosterone (79 +/- 8 vs. 60 +/- 6 pmol/l, p less than 0.05), cortisol (406 +/- 52 vs. 265 +/- 29 nmol/l, p less than 0.01), adrenaline (119 +/- 21 vs. 76 +/- 10 pg/ml, p less than 0.05), and noradrenaline (319 +/- 49 vs. 215 +/- 38 pg/ml, p less than 0.05) compared with time-matched placebo data. Converting enzyme inhibition, in the absence of major changes in blood pressure or renal blood flow, has little effect on ANF metabolism or renal bioactivity. However, ACE inhibition and ANF combined may interact to increase activity of the hypothalamo-pituitary-adrenal axis and sympathetic nervous system by unknown mechanisms.