Failure of probucol to prolong survival in salt-loaded stroke-prone spontaneously hypertensive rats.
We examined the effect of probucol, a lipid-lowering agent with strong antioxidant properties, on neurological events and survival in stroke-prone spontaneously hypertensive rats (SHRSP). Rapid onset of stroke was induced by maintaining the animals on 1% NaCl solution in place of drinking water. Probucol (10 or 30 mg/kg/day), both of which doses are therapeutic in humans was given by gastric gavage once daily to salt-loaded SHRSP. Animals receiving vehicle were used as controls. Probucol did not influence the elevation of blood pressure. Although probucol did not improve the survival rate of salt-loaded SHRSP, 30 mg/ kg/day of probucol slightly but significantly delayed the development of neurological events (p=0.0235 by generalized Wilcoxon test). However, a high dose of probucol (100 mg/kg/day) did not change the survival or neurological events of salt-loaded SHRSP. These results suggest that probucol may be protective against the development of neurological events, but is not preventive for the progression of stroke in SHRSP.
Miyashita
F
F
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Kawaguchi
A
A
Sugimoto
K
K
Kitoh
Y
Y
Tsutsumi
H
H
Fujimura
A
A
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D011341:Probucol / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D017211:Treatment Failure
D000924:Anticholesteremic Agents; D017673:Sodium Chloride, Dietary; D011341:Probucol