Proinflammatory cytokine inhibitor prolongs the survival of rats with heart failure induced by pressure overload.
Although an increased expression of proinflammatory cytokines has been reported in cardiac tissue samples from patients with congestive heart failure (CHF) and in various animal models of CHF, the role of these cytokines in the disease remains to be determined. Dahl salt-sensitive (DS) rats fed a high salt diet develop hypertension, cardiac hypertrophy and eventually CHF. In the present study, DS rats were treated with FR167653 (1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8-(4-pyridyl)pyrazolo[5,1-c][1,2,4]triazin-2-yl]-2-phenylethanedione sulfate monohydrate), a new low molecular weight inflammatory cytokine inhibitor. Treatment with 10 mg/kg per day of FR167653 significantly prolonged the survival of the animals and also prevented the bodyweight loss associated with heart failure. In conclusion, a non-peptide proinflammatory cytokine inhibitor improved the survival of animals with heart failure.
Shioi
T
T
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan.
Matsumori
A
A
Kakio
T
T
Kihara
Y
Y
Sasayama
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D006332:Cardiomegaly / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D004195:Disease Models, Animal; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy; D008297:Male; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D015996:Survival Rate; D015431:Weight Loss / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; C104334:FR 167653; D011720:Pyrazoles; D011725:Pyridines