RT Journal Article
T1 Trans-4-methoxy-β-nitrostyrene relaxes rat thoracic aorta through a sGC-dependent pathway
A1 Arruda-Barbosa, Loeste
A1 Teófilo, Taylena Maria
A1 Pinto Duarte, Gloria
A1 Lima Vale, Joyce Karen
A1 Dos Santos Borges, Rosivaldo
A1 Pedro Jorge Caldas Magalhães, 
A1 Lahlou, Saad
A1 Vasconcelos De Souza Neto, Francisco Das
AB 1-Nitro-2-phenylethene (NPe) induces a more potent vasorelaxant effect in rat aorta than its structural analog 1-nitro-2-phenylethane, but mediated through a different mechanism, independent of soluble guanylate cyclase (sGC) stimulation. We hypothesized that introducing an electron donor into the aromatic moiety might stabilize NPe, enhancing its potency and/or interaction with sGC. Therefore, trans-4-methoxy-β-nitrostyrene (T4MN) was synthesized, and mechanisms underlying its vasorelaxant effects were studied in rat aortic ring preparations. In endothelium-intact preparations, T4MN fully relaxed contractions induced by phenylephrine (PHE) with a potency similar to that of its parent drug, NPe. This vasorelaxant effect that was unchanged by endothelium removal, pretreatment with L-NAME, indomethacin, or MDL-12,330A, but was significantly reduced by tetraethylammonium, 4-aminopyridine, methyl blue, or ODQ. Under Ca2+-free conditions, T4MN did not alter contractions evoked by caffeine, but significantly reduced, in an ODQ-preventable manner, those induced by either PHE or extracellular Ca2+ restoration following depletion of intracellular Ca2+ stores in thapsigargin-treated aortic preparations. Under the same conditions, T4MN also reduced contractions induced by protein kinase C activator phorbol-12,13-dibutyrate with a potency similar to that evoked by this nitroderivative against PHE-induced contractions. In conclusion, T4MN induces potent vasorelaxation in rat aorta by stimulating the sGC-cGMP pathway through a NO-independent mechanism. Introduction of a methoxy group into the aromatic moiety apparently stabilizes NPe, thereby enhancing its interaction with sGC.
PB Elsevier
SN 0014-2999
YR 2017
FD 2017-07
LK https://hdl.handle.net/20.500.14352/115944
UL https://hdl.handle.net/20.500.14352/115944
LA eng
NO Arruda-Barbosa L, Teófilo TM, Souza-Neto FCV, Duarte GP, Vale JKL, Borges RS, Magalhães PJC, Lahlou S, Lahlou S. Corrigendum to Trans-4-methoxy-β-nitrostyrene relaxes rat thoracic aorta through a sGC-dependent pathway: European Journal of Pharmacology 807 (2017) 182-189. Eur J Pharmacol. 2018 Jan 15;819:291. doi: 10.1016/j.ejphar.2017.12.045. Erratum for: Eur J Pharmacol. 2017 Jul 15;807:182-189. doi: 10.1016/j.ejphar.2017.05.007. PMID: 29325909.
NO Conselho Nacional de Pesquisa, Brasil
NO Fundação Amazônica de Amparo a Estudos e Pesquisas, Brasil
DS Docta Complutense
RD 9 abr 2025