Effects of aminoguanidine and meloxicam on nitric oxide and prostaglandin E production induced by lipopolysaccharide in the hypothalamus and anterior pituitary of the rat.

MOHN, C; LOMNICZI, A; FALLETI, A; SCORTICATI, C; ELVERDIN, JC; MCCANN, S; RETTORI, V

NEUROIMMUNOMODULATION.

Karger AG

Lugar: Suiza; Año: 2001 p. 276 - 285

1021-7401

BACKGROUND/OBJECTIVE: Injection of bacterial lipopolysaccharide (LPS) into male rats activates genes that in turn induce many enzymes that participate in the animals´ response to LPS. There is induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in many tissues. This induction could result from combination with cell surface LPS receptors that directly induce both genes, or the nitric oxide (NO) released as a result of iNOS induction could induce COX-2. METHODS: To distinguish between these two possibilities, specific inhibitors of iNOS and COX-2 activity, aminoguanidine (AG) and meloxicam (MLX), respectively, were injected either peripherally or intracerebroventricularly (i.c.v.), and their effect on NO and prostaglandin E (PGE) production induced by LPS in the medial basal hypothalamus (MBH) and anterior pituitary gland (AP) were determined. RESULTS: Peripheral injection of AG blocked iNOS-derived NO production in the AP but not in the MBH. When AG was injected i.c.v., iNOS-derived NO production in the MBH was blocked. MLX injected peripherally blocked COX-2-derived PGE(2) production in the MBH and AP, whereas AG injected peripherally or i.c.v. was ineffective. Since AG was only effective in blocking iNOS-derived NO production in the MBH when injected i.c.v., AG apparently does not effectively cross the blood brain barrier, whereas MLX injected peripherally inhibited PGE production, probably by inhibiting COX-2 activity in both the MBH and AP. AG was ineffective in preventing the increase in PGE derived from COX-2 in either the MBH or AP. CONCLUSION: LPS directly induces both enzymes, iNOS and COX-2, in the hypothalamus and AP. Copyright 2002 S. Karger AG, Basel