Effect of the platelet activating factor antagonist (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride on endotoxin-induced hypotension and hematological parameters in rats.

The intravenous administration of endotoxin to anesthetized rats resulted in different hypotensive reactions depending on its dosage. More than 10 mg/kg of endotoxin induced biphasic hypotension; the first phase consisted in a small and transient depression (approximately 15 mmHg) of mean arterial pressure occurred within 1 min after the administration, and the second phase was a large and sustained depression (maximally 40 mmHg) observed from 1 h after the injection. At less than 3 mg/kg of endotoxin, the first phase of hypotension did not occur whereas the second phase of hypotension was observed. Pre-treatment or post-treatment with a specific platelet activating factor (PAF) antagonist, SM-12502 ((+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl, CAS 119383-00-5) inhibited the second phase of endotoxin (1 mg/kg)-induced hypotension. In addition, post-treatment with another PAF antagonist, (3-(4-(2-chlorophenyl)-9-methyl-6H-thieno (3,2-f) (1, 2,4)-thiazolo-phenone) also inhibited the second phase of hypotension. Blood PAF-like substance level, measured by the PAF radioimmunoassay, slightly increased at 1 min after administration of endotoxin (30 mg/kg). At 90 min after the injection, endotoxin (1 mg/kg) induced a significant increase of PAF-like substance level.(ABSTRACT TRUNCATED AT 250 WORDS)