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 alpha 1 adrenoreceptors 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+ and 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 less than 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 less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Active sodium-urea counter-transport is inducible in the basolateral membrane of rat renal initial inner medullary collecting ducts.

“…The response to furosemide administration is transient with significant changes in urinary excretion at 3-4 d that resolve at 7 d (Tables I and III). The time course and response we observed in rats is similar to the response in humans (26)(27)(28).…”

Interaction Between the Sodium‐Glucose–Linked Transporter 2 Inhibitor Dapagliflozin and the Loop Diuretic Bumetanide in Normal Human Subjects

“…An adaptive increase in proximal tubular Na + transporters could account for the increased Na + excretion after blockade of proximal SGLT2 by dapagliflozin after adaptation to bumetanide. PRA was doubled by 1 week of diuretics, as previously described,14, 18, 25, 29 whereas it was unchanged by dapagliflozin alone or by addition of dapagliflozin to bumetanide. This may be important because an increase in PRA and angiotensin II can increase protein excretion in CHF that enhances the activity of the collecting duct epithelial sodium channel and thereby enhances Na + reabsorption 30.…”

“…This “diuretic braking phenomenon”14 ultimately leaves many patients with CHF with an expanded blood volume that predicts adverse outcomes 15. Thus, new strategies for treatment of Na + retention are needed 13, 16, 17, 18, 19…”

Interactions Between Furosemide and the Renal Sympathetic Nerves

“…No data is currently available on effects of pharmacological blockade on regional blood flow changes during furosemide diuresis in humans. However, Wilcox et al (1987) reported that mean arterial pressure (MAP) decreased during furosemide diuresis in normal subjects pretreated with prazosin and captopril, whereas arterial pressure was unchanged during furosemide diuresis in absence of pharmacological blockade or in subjects pretreated with prazosin alone. These data suggest that angiotensin I1 may play an important role for the increase in peripheral resistance during furosemide administration in humans.…”

“…Similar findings have been reported during bumetanide diuresis in humans (Staalsen & Steiness 1990;Almeshari et al 1993). Postdiuretic Na retention is most pronounced during high dietary NaCl intake where it compensates entirely for the initial Na losses so that Na balance remains neutral from the first day of therapy (Bosch et al 1977;Kahn et al 1980;Wilcox et al 1983Wilcox et al & 1987. However, during dietary NaCl restriction, postdiuretic Na retention cannot compensate for the Na losses and a negative Na balance ensues .…”