Doxorubicin, an RNA synthesis inhibitor, prevents vasoconstriction and inhibits aberrant expression of endothelin-1 in the cerebral vasospasm model of the rat.

A vasoconstrictor peptide, endothelin-1 (ET-1), has been identified as one of the causative substances in cerebral vasospasm after subarachnoid hemorrhage. We investigated whether doxorubicin, an RNA synthesis inhibitor, effectively suppresses induction of ET-1 in the rat vasospasm model. Blood was injected around the right femoral artery and the left one was used as an internal control. Seven days later (day 7), diameters of the right femoral arteries narrowed to about 60% and this vasoconstriction was prevented by clinical dose (0.6 mg/kg) or one third of its dose of doxorubicin injected on day 1. Reverse transcriptase-polymerase chain reaction analysis demonstrated that expression of ET-1 mRNA in the vasospastic artery was not detected in doxorubicin-treated rats. It is concluded that doxorubicin effectively inhibits aberrant expression of ET-1 in the vasospasm-destined artery in the rat.