Mechanisms underlying the relaxation caused by the sesquiterpene polygodial in vessels from rabbit and guinea-pig

The sesquiterpene polygodial produces graded relaxation in rings of rabbit pulmonary artery or thoracic aorta and guinea-pig pulmonary artery with end othelium. In rings with rubbed endothelium its vasorelaxant action was larg ely reduced. The N-omega-nitro-L-arginine (L-NOARG), N-G-nitro-L-arginine m ethyl ester (L-NAME), 6-anilino-5,8-quinolinedione (LY 83583) and 1H-[1,2,4 ]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), inhibited the endothelium-depende nt vasorelaxant action of polygodial. In contrast, N-omega-nitro-D-arginine (D-NOARG). indomethncin, N-2-[(4R)-4-hydroxy-1-(1methyl-1H-indol-3yl)carbo nyl-L-prolyl]-N-methyl-N-phenylmenthyl-3-(2-naphthyl)-L-alaninamide (FK 888 ), (S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichloropheny l)butyl]benzamide (SR 48968), (8R, 9S, 11S)-(-)-9-hydroxy-9-n-hexyloxy-carb onyl-8-methyl-2,3,9,20-tetrahydro-8,11-epoxy-1H,8H,11N-2,7b,11a-triaqzadibe nzo [a, g]cycloocta[c, d, e]-trinden-1-one (KT 5720), calcitocin gene-relat ed peptide receptor antagonist (CGRP-(8-37), apamin, charybdotoxin and 4-am inopyridine had no effect on polygodial action. However, glibenclamide inhi bited partially, but significantly, its relaxant responses. These results d emonstrate that the vasorelaxation of polygodial is partly dependent on the release of nitric oxide (NO)or an NO-derived substance from the vascular e ndothelium through an activation of a guanylyl cyclase-dependent mechanism. Finally, results demonstrate that the polygodial vasorelaxant action is no t related with the opening of potassium (K+) channels, release of prostacyc lin, substance P, or with the activation of adenylyl cyclase-dependent mech anisms. (C) 1999 Elsevier Science B.V. All rights reserved.