AT(1) RECEPTOR SUBTYPE MEDIATES THE INHIBITORY EFFECT OF CENTRAL ANGIOTENSIN-II ON CEREBROSPINAL-FLUID FORMATION IN THE RAT

The effect of central administration of angiotensin II (All) on cerebr ospinal fluid (CSF) formation was studied in pentobarbital-anesthetize d, artificially-ventilated rats. CSF production was measured by the ve ntriculocisternal perfusion method with Blue Dextran 2000 as the indic ator. Baseline value of CSF production was 3.35 +/- 0.08 mu l/min. Int ra-cerebroventricular (i.c.v.) infusion of AII al rates of 0.5 and 5 p g/min significantly lowered (P<0.01) CSF formation by 23% and 16%, res pectively. In comparison, high peptide doses (50 and 500 pg/min) did n ot alter this parameter. The inhibitory effect of low AII doses on CSF formation was blocked by the i.c.v. AT(1) receptor subtype antagonist s, losartan and SK&F 108566 (2.4 and 2.7 ng/min, respectively), but no t by the AT(2) receptor subtype-specific agent, PD 123319 (3.8 ng/min) . Peptide AII antagonist, [Sar(1),Ile(8)]AII (5 ng/min), which binds t o both AT(1) and AT(2) receptors, had a similar effect to those of AT( 1)-specific blockers. It is concluded that AII, by controlling CSF for mation, may influence the water and electrolyte balance in the brain.