ANTIHYPERTENSIVE ACTION OF NON-NATRIURETIC DOSES OF FUROSEMIDE IN DAHL SALT-SENSITIVE RATS

Background That non-natriuretic doses of loop diuretics exert an antih ypertensive action has been suggested, but not confirmed, by simultane ous measurements of the arterial pressure and sodium balance during th erapy. Objective To examine the relationship between changes in arteri al pressure and changes in sodium balance during furosemide treatment. Design Twenty hypertensive Dahl salt-sensitive rats fed a 4% NaCl die t were allocated to four groups and administered the following treatme nts: placebo once a day intraperitoneally, continuous infusion of 4 mg /day furosemide intraperitoneally, 4 mg furosemide once a day intraper itoneally and 12 mg furosemide once every third day intraperitoneally. Methods The mean arterial pressure (MAP) was measured continuously wi th radiotelemetry and the sodium balance was measured with the rats in metabolic cages.Results Administration of furosemide as a bolus injec tion once a day (P < 0.01) or once every third day (P < 0.05) lowered the MAP significantly compared with placebo, whereas continuous infusi on of furosemide had no significant effect on the MAP (P < 0.07). Fast Fourier transformation analysis detected an acute antihypertensive ac tion related to the temporary diuretic and natriuretic responses durin g 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, extra cellular fluid volume, total body sodium and potassium were similar fo r rats in all groups. Conclusions Furosemide has an acute antihyperten sive action in Dahl salt-sensitive rats fed a 4% NaCl diet that is rel ated to renal sodium and volume losses whereas the long-term antihyper tensive effect is independent of changes in extracellular fluid volume , total body water, sodium and potassium.