BRAIN ANG-II AND PROSTAGLANDINS MEDIATE THE PRESSOR-RESPONSE AFTER CENTRAL BLOCKADE OF NITRIC-OXIDE SYNTHASE

Central inhibition of nitric oxide synthase (NOS) by intracerebroventr icular (i.c.v.) administration of N-G-nitro-L-arginine methyl ester (L -NAME; 150 mu g/5 mu l) to conscious rats produced a biphasic presser response characterized by an initial transient increase within 5 min, and a delayed response starting between 60-90 min. The effect was ster eospecific, as D-NAME (250 mu g/5 mu l) did not modify the resting art erial blood pressure, nor did L-arginine (323 mu g/5 mu l, i.c.v.), in dicating the substrate for NOS is not rate-limiting. Intracerebroventr icular pretreatment with losartan (25 mu g/5 mu l), a non-peptide anta gonist of the angiotensin II AT(1) receptor subtype, or indomethacin ( 100 mu g/5 mu l), a blocker of cyclooxygenase, however, prevented the initial increase in blood pressure without affecting the delayed press er response. In contrast, neither intravenous losartan (10 mg/kg b.wt) nor prazosin, an alpha(1) adrenergic receptor antagonist, at doses of 5 mu g/5 mu l (i.c.v.) or 0.3 mg/kg b.wt (i.v.) were effective in alt ering the presser responses. These results indicate that centrally pro duced NO maintains the resting arterial blood pressure at least partia lly through modulation of the brain angiotensin system and prostagland ins. (C) 1998 Elsevier Science B.V.