Brain ANG II and prostaglandins mediate the pressor response after central blockade of nitric oxide synthase

Central inhibition of nitric oxide synthase (NOS) by intracerebroventricular (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 stereospecific, as D-NAME (250 mu g/5 mu l) did not modify the resting arterial blood pressure, nor did L-arginine (323 mu g/5 mu l, i.c.v.), indicating the substrate for NOS is not rate-limiting. Intracerebroventricular pretreatment with losartan (25 mu g/5 mu l), a non-peptide antagonist 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 presser 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 altering the presser responses. These results indicate that centrally produced NO maintains the resting arterial blood pressure at least partially through modulation of the brain angiotensin system and prostaglandins. (C) 1998 Elsevier Science B.V.