SEXUAL DIFFERENCES IN THE RELAXANT EFFECTS OF ANANDAMIDE IN THE RAT MESENTERIC BED: PARTICIPATION OF CGRP AND PROSTACYCLIN.

PERONI R, ORLIAC ML, ABRAMOFF T, RIBEIRO ML*, FRANCHI AM* AND ADLER-GRASCHINSKY E.

Atlanta , USA

Congreso; 36th Annual Meeting of the Society for Neuroscience; 2006

Society for Neuroscience

SEXUAL DIFFERENCES IN THE RELAXANT EFFECTS OF ANANDAMIDE IN THE RAT MESENTERIC BED: PARTICIPATION OF CGRP AND PROSTACYCLIN. Peroni R, Orliac ML, Abramoff T, Ribeiro ML*, Franchi AM* and Adler-Graschinsky E. ININFA and CEFyBO* (CONICET), Buenos Aires, ARGENTINA. rperoni@ffyb.uba.ar This work was addressed to study the mechanisms involved in the greater relaxations caused by anandamide (AEA) in mesenteric beds isolated from female compared to male rats (Peroni et al., Eur. J. Pharmacol. 493:151, 2004). AEA effects were almost abolished by the nitric oxide synthase (NOS) inhibitor 100 mM L-NAME in intact as well as in de-endothelized male and female mesenteries and significantly reduced by the selective neuronal NOS inhibitor 5 mM Nw-propyl-L-arginine in intact arteries from either sex. Endothelial removal enhanced the reduction of vasoconstrictor responses to noradrenaline caused by AEA (0.01-10 mM) in mesenteric beds isolated from male and ovariectomized female but not from intact female rats. On the other hand, the irreversible endothelin ET-1 receptor antagonist 0.1 mM BQ610 decreased noradrenaline contractions only in males and this effect was abolished by endothelial removal. Sensory in vivo denervation markedly reduced the relaxation caused by AEA in either male or female mesenteries and also prevented the relaxant responses caused by the vanilloid TRPV1 receptor agonist capsaicin (0.01-10 mM) in either sex. The calcitonin gene related peptide (CGRP) content in rat mesenteric beds was higher in intact female than in male rats, faded by ovariectomy and restored to control values by chronic treatment with 17b-oestradiol. This latter procedure also increased CGRP content in males up to the same levels observed in females. With regard to prostanoids, the ratio prostacyclin / thromboxane A2 did not differ between males and females under control conditions but it was significantly reduced in male rats after exposure to AEA, due to the decrease in males of the relaxing prostacyclin. Moreover, the selective cyclooxygenase-2 inhibitor 0.1 mM NS-398 significantly interfered with the relaxations caused by AEA in female but not in male rats. It is proposed that the higher relaxations caused by AEA in the vasculature of female rats results from the contribution of relaxing factors such as CGRP and prostacyclin. Contractile factors, such as endothelin, could be involved in the lower effects of AEA in males. Supported by FONCYT, PICT 5-14107 and CONICET, PIP 5695.