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

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)

Hypotension and sinus arrest with exercise-induced hyperkalemia and combined verapamil/propranolol therapy.

A case of life-threatening hypotension due to sinus arrest is described in a patient in whom exercise-induced hyperkalemia developed during a stable regimen that included verapamil, propranolol, and ibuprofen. Renal and extrarenal handling of the endogenous potassium load induced by heat and exertion in this patient may have been compromised by the presence of ibuprofen and propranolol. When superimposed upon the negative chronotropic effects of verapamil and propranolol, the hyperkalemia precipitated sinus arrest. Clinicians should be aware of this potential metabolic-drug interaction in patients taking verapamil and/or propranolol who perform strenuous exercise in hot weather or who may be exposed to other hyperkalemic precipitants.

Comparative acceptance of three transdermal nitroglycerin placebo patches.

Factors that might affect patient acceptance of transdermal drug-delivery system patches were evaluated in healthy volunteers using placebo patches. Placebo transdermal nitroglycerin patches (Transderm-Nitro 5 placebo, Ciba Pharmaceutical Company; Nitro-Dur 10 cm2 placebo, Key Pharmaceuticals; and Nitrodisc 5 placebo, Searle Laboratories) were supplied by the manufacturers. Eighty-two healthy subjects were randomly assigned to begin using one of the three brands of patches. Using a Latin-square crossover design, subjects applied each brand of patch daily for five days and crossed over to the other brands on study days 6 and 11. At the end of each study phase, subjects completed a written questionnaire designed to evaluate their overall acceptance of each brand of patch. A total of 80 subjects completed all three phases of the study. According to forced rank preference, 84% of subjects preferred the Ciba patch to one of the other two brands. Subjects judged the Ciba patch to be the easiest of the three brands to use and reported significantly fewer side effects and skin irritation while using the Ciba patch; they also preferred the size of the Ciba patch and experienced significantly fewer problems with adherence of the Ciba patch. A significant percentage of subjects indicated that they would prefer a transdermal patch over tablets or ointment. Most subjects preferred the Ciba patch over the Key patch or Searle patch.

Factors affecting potassium balance during frusemide administration.

We investigated the effects of Na+ intake, the renin-angiotensin-aldosterone system and anti-diuretic hormone (ADH) on K+ balance during 3 days of frusemide administration to six normal subjects. Subjects received 40 mg of frusemide for 3 days during three different protocols: Na+ intake 270 mmol/day (high salt); Na+ intake 20 mmol/day to stimulate the renin-angiotensin-aldosterone system (low salt); Na+ intake 270 mmol/day plus captopril (25 mg/6 h) to prevent activation of the renin-angiotensin-aldosterone system. In a fourth protocol, a water load was given during high salt intake to prevent ADH release and then frusemide was given. During high salt intake, frusemide increased K+ excretion (UKV) over 3 h, but the loss was counterbalanced by subsequent renal K+ retention so that daily K+ balance was neutral. During low salt intake, the magnitude of the acute kaliuresis following the first dose of frusemide and the slope of the linear relationship between UKV and the log of frusemide excretion were increased compared with that found during the high salt intake. In addition, low salt intake abolished the compensatory renal retention of K+ after frusemide and cumulative K+ balance over 3 days of diuretic administration was uniformly negative (-86 +/- 7 mmol/3 days; P less than 0.001). Captopril abolished the rise in plasma aldosterone concentration induced by frusemide. The acute kaliuresis after frusemide was unchanged compared with that observed during high salt intake. The compensatory reduction in UKV occurring after the diuretic was slightly potentiated. In fact, captopril given without the diuretic induced a small positive K+ balance.(ABSTRACT TRUNCATED AT 250 WORDS)

Response of the kidney to furosemide. II. Effect of captopril on sodium balance.

We investigated the role of the renin-angiotensin-aldosterone (RAA) system during furosemide (F) administration. The effects of adding captopril (C) (25 mg . 6 hr-1) to F (40 mg daily for 3 days) were studied in six normal subjects equilibrated to a daily sodium (Na) intake of 270 mmoles. Without C, F produced a marked natriuresis but Na+ excretion fell sharply between drug doses. This resulted in neutral Na balance (+22 +/- 58 mmoles . 3 days-1; mean +/- SE). Plasma angiotensin (AII) and aldosterone (Aldo) rose, but mean blood pressure (MBP) was unaltered. C abolished the F-induced increases in AII and Aldo but did not modify the pattern of Na+ excretion. Na+ balance remained neutral (+42 +/- 54 mmoles . 3 days-1). With C alone, Na+ balance was positive (+110 +/- 30 mmoles . 3 days-1; P less than 0.02). In protocols C alone and F + C, MBP fell by a comparable amount. F alone and F + C increased plasma norepinephrine and prostaglandin E2 metabolite; these did not change with C alone. In conclusion, activation of the RAA system by F is not essential for the compensatory increase in Na+ reabsorption that maintains Na+ balance after F.(ABSTRACT TRUNCATED AT 250 WORDS)