Mechanisms Underlying Vasorelaxation Induced in Rat Aorta by Galetin 3,6-Dimethyl Ether, a Flavonoid from Piptadenia stipulacea (Benth.) Ducke
| Autor: | Ana Carolina de Carvalho Correia, C. L. Macêdo, Bárbara Viviana de Oliveira Santos, Italo R. R. Martins, Bagnólia Araújo da Silva, Daysianne Pereira de Lira, Fabiana de Andrade Cavalcante, Luiz Henrique César Vasconcelos |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Stereochemistry Pharmaceutical Science In Vitro Techniques Pharmacology Apamin Piperazines Sildenafil Citrate Article Analytical Chemistry Glibenclamide lcsh:QD241-441 Calcium Chloride Phenylephrine chemistry.chemical_compound Cyclic nucleotide lcsh:Organic chemistry Drug Discovery Potassium Channel Blockers medicine Animals Rats Wistar Physical and Theoretical Chemistry galetin 3 6-dimethyl ether vasodilator Aorta Flavonoids Sulfonamides calcium Voltage-dependent calcium channel Inward-rectifier potassium ion channel Organic Chemistry Phosphodiesterase ion channels Fabaceae Aminophylline Myocardial Contraction Vasodilation Verapamil chemistry Purines Chemistry (miscellaneous) Molecular Medicine Milrinone phosphodiesterase medicine.drug |
| Zdroj: | Molecules, Vol 19, Iss 12, Pp 19678-19695 (2014) Molecules Volume 19 Issue 12 Pages 19678-19695 |
| ISSN: | 1420-3049 |
| Popis: | In this study, we investigated the relaxant action of galetin 3,6-dimethyl ether (FGAL) on rat aorta. The flavonoid relaxed both PMA‑ and phenylephrine (Phe)-induced contractions (pD2 = 5.36 ± 0.11 and 4.17 ± 0.10, respectively), suggesting the involvement of PKC and Phe pathways or α1 adrenergic receptor blockade. FGAL inhibited and rightward shifted Phe-induced cumulative concentration‑response curves, indicating a noncompetitive antagonism of α1 adrenergic receptors. The flavonoid was more potent in relaxing 30 mM KCl- than 80 mM KCl-induced contractions (pD2 = 5.50 ± 0.22 and 4.37 ± 0.12). The vasorelaxant potency of FGAL on Phe-induced contraction was reduced in the presence of 10 mM TEA+. Furthermore, in the presence of apamin, glibenclamide, BaCl2 or 4-AP, FGAL-induced relaxation was attenuated, indicating the participation of small conductance calcium-activated K+ channels (SKCa), ATP-sensitive K+ channels (KATP), inward rectifier K+ channels (Kir) and voltage-dependent K+ channels (KV), respectively. FGAL inhibited and rightward shifted CaCl2-induced cumulative concentration-response curves in both depolarizing medium (high K+) and in the presence of verapamil and phenylephrine, suggesting inhibition of Ca2+ influx through voltage-gated calcium channels (CaV) and receptor operated channels (ROCs), respectively. Likewise, FGAL inhibited Phe-induced contractions in Ca2+-free medium, indicating inhibition of Ca2+ release from the sarcoplasmic reticulum (SR). FGAL potentiated the relaxant effect of aminophylline and sildenafil but not milrinone, suggesting the involvement of phosphodiesterase V (PDE V). Thus, the FGAL vasorelaxant mechanism involves noncompetitive antagonism of α1 adrenergic receptors, the non-selective opening of K+ channels, inhibition of Ca2+ influx through CaV or ROCs and the inhibition of intracellular Ca2+ release. Additionally, there is the involvement of cyclic nucleotide pathway, particularly through PDE V inhibition. |
| Databáze: | OpenAIRE |
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