PT  - JOURNAL ARTICLE
AU  - Orliac, Marı́a Luz
AU  - Peroni, Roxana
AU  - Celuch, Stella M
AU  - Adler-Graschinsky, Edda
TI  - Potentiation of Anandamide Effects in Mesenteric Beds Isolated from Endotoxemic Rats
AID  - 10.1124/jpet.102.041095
DP  - 2003 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 179--184
VI  - 304
IP  - 1
4099  - http://jpet.aspetjournals.org/content/304/1/179.short
4100  - http://jpet.aspetjournals.org/content/304/1/179.full
SO  - J Pharmacol Exp Ther2003 Jan 01; 304
AB  - The aim of the present experiments was to study the effects of exogenously added anandamide on transient norepinephrine (NE)-induced contractions in mesenteric beds isolated from adult male Sprague-Dawley rats 6 h after the i.p. administration of 5 mg kg−1lipopolysaccharide (LPS). LPS treatment induced a 3-fold increase in total nitric-oxide synthase (NOS) activity without modifying either the systolic blood pressure or the vascular reactivity to NE of the isolated mesenteric bed. The endocannabinoid anandamide (0.01–10 μM) caused concentration-dependent reductions of the contractile responses to NE in the isolated mesenteric bed. This effect was significantly potentiated after LPS treatment compared with the controls. Anandamide-induced reductions of the contractile responses to NE in mesenteric beds isolated from LPS-treated rats were unmodified by endothelium removal but significantly diminished by either the anandamide amidase inhibitor phenylmethylsulfonyl fluoride (200 μM) or the vanilloid receptor antagonist capsazepine (1 μM). The vanilloid receptor agonist capsaicin (0.01–100 nM) also caused concentration-dependent relaxations that were potentiated in mesenteric beds from LPS-treated rats. Nevertheless, they were unmodified by 1 μM capsazepine. It is concluded that the potentiation of anandamide relaxations after LPS treatment, which are evident at early stages of endotoxic shock, could involve the participation of an anandamide metabolite and might be mediated, at least in part, through a vanilloid receptor. The American Society for Pharmacology and Experimental Therapeutics