Effect of endothelin on production of cerebrospinal fluid in rabbits.

BACKGROUND AND PURPOSE Endothelin is a potent vasoconstrictor in several tissues, including the choroid plexus. The goal of this study was to determine whether endothelin affects the production of cerebrospinal fluid. METHODS Ventriculocisternal perfusion was used to measure the production of cerebrospinal fluid in anesthetized rabbits. Changes in production of cerebrospinal fluid were examined in response to vehicle, intravenous endothelin (alone and in the presence of indomethacin), and intraventricular endothelin. RESULTS Under control conditions, the reduction in production of cerebrospinal fluid in response to endothelin administered intravenously was only modestly greater than that during infusion of vehicle. Because endothelin releases cyclooxygenase products that attenuate the direct effects of endothelin in several tissues, effects of endothelin on the production of cerebrospinal fluid were also examined after inhibition of cyclooxygenase. Production of cerebrospinal fluid in response to 1 micrograms/kg i.v. endothelin was reduced more in animals treated with indomethacin than in untreated animals (-34 +/- 7% [mean +/- SEM] versus -14 +/- 6%, p less than 0.05). Thus, effects of endothelin on the production of cerebrospinal fluid are attenuated by cyclooxygenase products. Finally, responses to intraventricular endothelin were examined. Intraventricular endothelin produced a modest, but significant, reduction in the production of cerebrospinal fluid. CONCLUSIONS In summary, endothelin may play a role in regulation of the brain fluid balance by affecting the rate of production of cerebrospinal fluid, and this effect is modulated by cyclooxygenase products.