Antihypertensive action of non-natriuretic doses of furosemide in Dahl salt-sensitive rats

BACKGROUND: That non-natriuretic doses of loop diuretics exert an antihypertensive action has been suggested, but not confirmed, by simultaneous measurements of the arterial pressure and sodium balance during therapy. OBJECTIVE: To examine the relationship between changes in arterial pressure and changes in sodium balance during furosemide treatment. DESIGN: Twenty hypertensive Dahl salt-sensitive rats fed a 4% NaCl diet were allocated to four groups and administered the following treatments: placebo once a day intraperitoneally, continuous infusion of 4 mg/day furosemide intraperitoneally, 4 mg furosemide once a day intraperitoneally and 12 mg furosemide once every third day intraperitoneally. METHODS: The mean arterial pressure (MAP) was measured continuously with radiotelemetry and the sodium balance was measured with the rats in metabolic cages. RESULTS: Administration of furosemide as a bolus injection once a day (P < 0.01) or once every third day (P < 0.05) lowered the MAP significantly compared with placebo, whereas continuous infusion of furosemide had no significant effect on the MAP (P < 0.07). Fast Fourier transformation analysis detected an acute antihypertensive action related to the temporary diuretic and natriuretic responses during the period 0-6 h after intraperitoneal bolus injections of 4 and 12 mg furosemide. None of the treatment regimens produced 24 h sodium or potassium losses. At the end of the study, the total body water, extracellular fluid volume, total body sodium and potassium were similar for rats in all groups. CONCLUSIONS: Furosemide has an acute antihypertensive action in Dahl salt-sensitive rats fed a 4% NaCl diet that is related to renal sodium and volume losses whereas the long-term antihypertensive effect is independent of changes in extracellular fluid volume, total body water, sodium and potassium.