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 endothelium. In rings with rubbed endothelium its vasorelaxant action was largely reduced. The N(omega)-nitro-L-arginine (L-NOARG), N(G)-nitro-L-arginine methyl 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-dependent vasorelaxant action of polygodial. In contrast, N(omega)-nitro-D-arginine (D-NOARG), indomethacin, N(2)-[(4R)-4-hydroxy-1-(1methyl-1H-indol-3yl)carbonyl-L-prol yl]-N-met hyl-N-phenylmethyl-3-(2-naphthyl)-L-alaninamide (FK 888), (S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3, 4-dichlorophenyl)butyl]benzamide (SR 48968), (8R,9S, 11S)-(-)-9-hydroxy-9-n-hexyloxy-carbonyl-8-methyl-2,3,9, 20-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triaqzadibenzo[a, g]cycloocta[c,d,e]-trinden-1-one (KT 5720), calcitocin gene-related peptide receptor antagonist (CGRP-(8-37), apamin, charybdotoxin and 4-aminopyridine had no effect on polygodial action. However, glibenclamide inhibited partially, but significantly, its relaxant responses. These results demonstrate that the vasorelaxation of polygodial is partly dependent on the release of nitric oxide (NO )or an NO-derived substance from the vascular endothelium through an activation of a guanylyl cyclase-dependent mechanism. Finally, results demonstrate that the polygodial vasorelaxant action is not related with the opening of potassium (K(+)) channels, release of prostacyclin, substance P, or with the activation of adenylyl cyclase-dependent mechanisms.
André
E
E
Department of Pharmacology, Universidade Federal de Santa Catarina, CCB, Rua Ferreira Lima, 82, Florianópolis, Brazil.
Malheiros
A
A
Cechinel-Filho
V
V
Yunes
R A
RA
Calixto
J B
JB
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011651:Pulmonary Artery / Q000187:drug effects; D011817:Rabbits; D012717:Sesquiterpenes / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D020030:Nitric Oxide Donors; D026902:Potassium Channel Blockers; D012717:Sesquiterpenes; D014665:Vasodilator Agents; D009569:Nitric Oxide; C034380:polygodial; D006162:Guanylate Cyclase; D000109:Acetylcholine