Different effects of long- and short-acting loop diuretics on survival rate in Dahl high-salt heart failure model rats.
OBJECTIVE
We compared therapeutic effects of furosemide, a short-acting loop diuretic, and azosemide, a long-acting one, in hypertensive heart failure rats to test the hypothesis that long-acting diuretics are superior to short-acting types in heart failure.


METHODS
Dahl salt-sensitive rats fed an 8% NaCl diet from age 8 weeks were divided at age 21 weeks (compensated hypertrophic stage) into three groups: rats treated with furosemide (40 mg/kg/day), those treated with azosemide (80 mg/kg/day) and untreated rats. Rats fed a 0.3% NaCl diet served as controls.


RESULTS
Both medications prevented left ventricular systolic dysfunction and enlargement at age 31 weeks, and attenuated macrophage infiltration, reactive oxygen species generation, and gelatinolytic activity to the same degree. Azosemide suppressed left ventricular fibrosis to the control level, but furosemide did not. Azosemide ameliorated myocardial catecholamine depletion and improved survival rate. Furosemide increased plasma norepinephrine levels and did not exert such beneficial effects.


CONCLUSIONS
Azosemide provided better prognosis in heart failure rats compared with furosemide, partly through attenuation of the reflex increase in cardiac sympathetic neuronal activity caused by the development of heart failure. The current findings suggest a need for clinical trials examining whether long- and short-acting diuretics provide a different prognosis in patients with heart failure.
Department of Cardiovascular Medicine, (A8) Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Japan.
Junichi
J
Yoshida
Kazuhiro
K
Yamamoto
Toshiaki
T
Mano
Yasushi
Y
Sakata
Mayu
M
Nishio
Tomohito
T
Ohtani
Masatsugu
M
Hori
Takeshi
T
Miwa
Tohru
T
Masuyama
D000818:Animals; D004452:Echocardiography; D005665:Furosemide / Q000494:pharmacology / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D007375:Interleukin-1 / Q000235:genetics; D009638:Norepinephrine / Q000032:analysis / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D013424:Sulfanilamides / Q000494:pharmacology / Q000627:therapeutic use*; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000235:genetics; D016896:Treatment Outcome; D020257:Ventricular Remodeling; D013777:Tetrazoles; D013876:Thiophenes; D000096926:Benzenesulfonamides
D005665:Furosemide; D007375:Interleukin-1; D009638:Norepinephrine; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D049994:Sodium Potassium Chloride Symporter Inhibitors; D013424:Sulfanilamides; D016212:Transforming Growth Factor beta; C018222:azosemide; D013777:Tetrazoles; D013876:Thiophenes; D000096926:Benzenesulfonamides