Endothelium-dependent relaxation of rat mesenteric arterial rings by a Phoneutria nigriventer venom fraction.
Phoneutria nigriventer spider venom has been described as acting on several cardiovascular sites. In the present paper, a semi-purified fraction of this spider venom was studied to observe any contractile or relaxing effect in rat mesenteric arterial rings (MAR). Spider venom was first fractionated by gel filtration and subsequently by gradual isocratic steps in 0.1% trifluoroacetic acid. The first fraction of this last fractionation step is studied in the present paper and due to its main effect, it was named NORF (nitric oxide releasing fraction). No direct contractile effect was induced by NORF in relaxed MAR, suggesting no NORF-induced neurotransmitter release in this preparation. No significant influence of NORF was observed on concentration-response curves to phenylephrine on endothelium-denuded MAR, but a significant inhibitory shift of concentration-respense curves was observed on endothelium-preserved MAR (EC50 = 0.39 +/- 0.07 microM for control and EC50 = 0.68 +/- 0.14 microM with NORF). NORF induced concentration-dependent relaxation in endothelium-preserved phenylephrine pre-contracted MAR but not in endothelium-denuded MAR. NORF-induced relaxation was inhibited by the nitric oxide synthase inhibitor L-NAME (N(omega)-nitro-arginine methyl ester). Indomethacin or HOE-140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin) had no significant effect on NORF-induced relaxation. Acetylcholine- and NORF-induced relaxation of pre-contracted MAR were differently inhibited by atropine. The pA2 value for atropine-acetylcholine was 9.78 +/- 0.06 and that for atropine-NORF was 8.53 +/- 0.30 (P<0.01). These observations suggest that NORF induces concentration-dependent liberation of nitric oxide from MAR endothelium and that a non-muscarinic mechanism might be involved in this effect. Our data suggest no involvement of prostanoids or bradykinin in the relaxing mechanism.
Weinberg
MariaLourdesDuarte
M
Department of Physiology and Biophysics, Universidade Federal de Minas Gerais, B. Horizonte, Brazil. weinberg@mono.icb.ufmg.br
Cordeiro
Marta Nascimento
MN
De
LimaMariaElena
L
Oliveira
Leida Calegário
LC
Diniz
Carlos Ribeiro
CR
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020030:Nitric Oxide Donors / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology*; D013112:Spiders; D014664:Vasodilation / Q000187:drug effects*
D020030:Nitric Oxide Donors; D013111:Spider Venoms; D010656:Phenylephrine; D009569:Nitric Oxide; D001285:Atropine; D000109:Acetylcholine; D001920:Bradykinin