Effect of aspirin treatment on the hypotensive effect of clonidine in rats.

Rats were pretreated with aspirin (5 mg/kg i.p. 5 days) or saline, anaesthetized with pentobarbitone, and blood pressure recorded from the carotid artery. Clonidine (30 micrograms/kg) was injected intravenously via a cannula inserted into the femoral vein. Aspirin pretreatment significantly reduced the hypotensive effect of clonidine. Spleen, heart brain, kidneys and lung were removed from the animals 60 min after clonidine administration. Prostaglandin biosynthesis from endogenous substrate was determined by homogenizing tissues (1:4 w/v) in either Tris buffer (pH 7.4) or in 1 M formic acid: ethanol (1:V/v). Prostaglandins were extracted into ethyl acetate and bioassayed on the rat stomach strip. Clonidine administration significantly increased the prostaglandin formation in heart, brain and kidney. Animals pretreated with aspirin showed a reduction in the clonidine-induced increase in prostaglandin synthesis in heart, brain and spleen. The results suggest that the hypotensive effect of clonidine in anaesthetized rats may in part be secondary to stimulation of central prostaglandin biosynthesis.