THE ROLE OF ANGIOTENSIN-II IN REGULATION OF CEREBROSPINAL-FLUID FORMATION IN RABBITS

The effect of central and peripheral administrations of angiotensin II (AII) on cerebrospinal fluid (CSF) formation was investigated in rabbits anesthetized with intravenous alpha-chloralose and urethane. CSF production was measured by the ventriculo-cisternal perfusion method with Blue dextran 2000 used as an indicator substance. AII infused intracerebroventricularly (i.c.v.) at rates of 5.5 and 55 pg min-1 significantly decreased CSF formation rate by 27% and 36%, respectively. This AII action could be completely blocked by simultaneously administered specific AII antagonist, [Sar1, Ala8]AII (saralasin), given i.c.v. at a rate of 5.5 ng min 1. Intracerebroventricular infusion of All at a rate of 5.5 ng min-1 did not change CSF production. Saralasin, when given alone into the ventricular system (5.5 ng min-1), non-significantly increased CSF production by 12%. However, in 4 of the 6 animals studied, the rise in CSF production was statistically significant (by 23%). Intravenous infusion of All at rates of 30 and 100 ng kg-1 min-1 was found not to change CSF formation rate. Also, i.c.v. administration of angiotensin I converting enzyme inhibitor, captopril (10 mul min-1), did not influence CSF production. It is concluded that the centrally released All can control CSF production. Our results suggest that under normal conditions, All exerts a tonic inhibitory effect on CSF formation. In contrast, the blood-borne peptide seems not to influence this physiological process.