STUDY OF THE MECHANISMS UNDERLYING THE ENHANCED CARDIOVASCULAR RESPONSES TO ANANDAMIDE AFTER PROLONGED NOS INHIBITION

CELUCH SM*, ABRAMOFF T, GARCÍA MC, PERONI RN AND ADLER-GRASCHINSKY

Córdoba, Argentina

Congreso; XXX VIII Reunión Anual de la Asociacion Argentina de Farmacología Experimental; 2006

STUDY OF THE MECHANISMS UNDERLYING THE ENHANCED CARDIOVASCULAR RESPONSES TO ANANDAMIDE AFTER PROLONGED NOS INHIBITION Celuch SM*, Abramoff T, García MC, Peroni RN and Adler-Graschinsky E. *sceluch@ffyb.uba.ar ININFA (CONICET).  Junín 956, 5º. Buenos Aires-Argentina. In Sprague-Dawley rats the vasorelaxant effect of anandamide (AEA: 1; 5 and 10 mM) in isolated mesenteric beds as well as the hypotensive responses to i.v. administered AEA (5 mg/kg) were potentiated by chronic treatment with the nitric oxide synthase (NOS) inhibitor Nw-nitro-L-arginine-methyl ester (L-NAME; 40 mg/100 ml in the drinking water; 4 weeks). Since the vascular relaxation caused by AEA is related to the activation of vanilloid receptors (TRPV1) and the release of calcitonin gene-related peptide (CGRP) from perivascular sensory nerve endings, this study examined whether increases in either TRPV1 expression or tissue CGRP content could participate in the enhanced depressor effects of AEA observed after long-term inhibition of NOS. In the tongue, used as a representative model of TRPV1 protein, the receptor expression was 60% lower in rats chronically treated with L-NAME than in untreated rats (p<0.001). CGRP-like immunoreactivity in mesenteric arteries did not change after L-NAME treatment. It is concluded that the enhanced depressor responses to AEA in L-NAME treated rats is unrelated to either overexpression of TRPV1 receptors or increased CGRP content in vascular tissue. Supported by FONCYT, PICT 5-14107 and CONICET, PIP 5695.