Na+, K+, and BP homeostasis in man during furosemide: Effects of prazosin and captopril

Abstract

Furosemide increases sodium (Na+) and potassium (K+) excretion but if dietary salt is provided, a compensatory reduction in Na+ and K+ excretion follows which restores neutral balances within 18 to 24 hours. This compensation is not interrupted by blockade of the renin-angiotensin-aldosterone system (RAA) alone with captopril. Since plasma norepinephrine concentration increases after furosemide and alpha1 adrenoceptors can mediate enhanced Na+ reabsorption, we administered prazosin (2 mg 6 hr-1) to six normal volunteers consuming a daily intake of 270 mmol of Na+ an 75 mmol of K+, and added captopril (25 mg 6 hr-1) for an additional day to block the RAA system concurrently. Furosemide (40 mg day-1) was given for the last four days. Prazosin given alone before the diuretic reduced (P < 0.05) BP and plasma angiotensin II (AII) concentration and increased body weight and heart rate. However, when given with furosemide, neither prazosin nor prazosin with captopril modified the short-term natriuretic or kaliuretic responses to furosemide, or the ensuing compensatory reductions in Na+ and K+ excretion. Accordingly, cumulative balances for Na+ and K+ remained neutral over four days of diuretic administration. Neither drug altered the renal responsiveness to the diuretic which was assessed from the relationship between renal Na+ and K+ excretion and diuretic elimination. Although the BP was maintained when furosemide was given alone, when given with prazosin and captopril, the mean BP fell by 13 ± 5 mm Hg (P < 0.05). In conclusion, in normal human subjects consuming a liberal salt intake, neither the alpha1 adrenoreceptor nor the RAA systems are required for maintenance of Na+ and K+ balances during administration of furosemide.