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.


METHODS
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.
Haugan
K
K
Department of Pharmacology, University of Copenhagen, Denmark.
Petersen
J S
JS
Spannow
J
J
Shalmi
M
M
Christensen
S
S
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000008:administration & dosage*; D004351:Drug Resistance; D005665:Furosemide / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects; D007263:Infusions, Parenteral; D007274:Injections, Intraperitoneal; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism; D012982:Sodium, Dietary / Q000633:toxicity; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000959:Antihypertensive Agents; D004232:Diuretics; D012982:Sodium, Dietary; D005665:Furosemide; D012964:Sodium; D011188:Potassium