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1 Centro de Regulación Celular y Patología J. V. Luco, Instituto MIFAB, Departmento de Fisiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Casilla Box 114-D, Santiago, Chile
2 Instituto de Investigaciones Farmacológicas, CONICET, Buenos Aires, Argentina
In the isolated rat mesenteric bed, the 1 min perfusion with 100 nM anandamide, a concentration that did not evoke vasorelaxation, elicited an acute release of 165.1 ± 9.2 pmol nitric oxide (NO) that was paralleled by a 2-fold increase in cGMP tissue levels. The rise in NO released was mimicked by either (R)-(+)-methanandamide or the vanilloid receptor agonists resiniferatoxin and (E)-capsaicin but not by its inactive cis-isomer (Z)-capsaicin. The NO release elicited by either anandamide or capsaicin was reduced by the TRPV1 receptor antagonists 5'-iodoresiniferatoxin, SB 366791 and capsazepine as well as by the cannabinoid CB1 receptor antagonists SR 141716A or AM251. The outflow of NO elicited by anandamide and capsaicin was also reduced by endothelium removal or NO synthase inhibition, suggesting the specific participation of endothelial TRPV1 receptors, rather than the novel endothelial TRPV4 receptors. Consistently, RT-PCR showed the expression of the mRNA coding for the rat TRPV1 receptor in the endothelial cell layer, in addition to its expression in sensory nerves. The participation of sensory nerves on the release of NO was precluded on the basis that neonatal denervation of the myenteric plexus sensory nerves did not modify the pattern of NO release induced by anandamide and capsaicin. We propose that low concentrations of anandamide, devoid of vasorelaxing effects, elicit an acute release of NO mediated predominantly by the activation of endothelial TRPV1 receptors whose physiological significance remains elusive.
(Received 6 July 2005;
accepted after revision 1 August 2005;
first published online 4 August 2005)
Corresponding author J. P. Huidobro-Toro: Departamento de Fisiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Casilla 14-D, Santiago, Chile. Email: jphuid{at}bio.puc.cl
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