Vasorelaxant effect of trans-4-chloro-β-nitrostyrene, a synthetic nitroderivative, in rat thoracic aorta.

Autor: Sousa-Brito HL; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil., Arruda-Barbosa L; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil., Vasconcelos-Silva AA; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil., Gonzaga-Costa K; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil., Duarte GP; Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil., Borges RS; Department of Pharmacy, Federal University of Pará, Belém, Brazil., Magalhães PJC; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil., Lahlou S; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil.
Jazyk: angličtina
Zdroj: Fundamental & clinical pharmacology [Fundam Clin Pharmacol] 2021 Apr; Vol. 35 (2), pp. 331-340. Date of Electronic Publication: 2020 Nov 13.
DOI: 10.1111/fcp.12624
Abstrakt: Previously, we showed that 1-nitro-2-phenylethene, a nitrostyrene derivative of 1-nitro-2-phenylethane, induced vasorelaxant effects in rat aorta preparations. Here, we studied mechanisms underlying the vasorelaxant effects of its structural analog, trans-4-chloro-β-nitrostyrene (T4CN), in rat aortic rings. Increasing concentrations of T4CN (0.54-544.69 µm) fully and similarly relaxed contractions induced by phenylephrine (PHE, 1 µm) or KCl (60 mm) in endothelium-intact aortic rings with IC 50 values of 66.74 [59.66-89.04] and 79.41 [39.92-158.01] µm, respectively. In both electromechanical and pharmacomechanical couplings, the vasorelaxant effects of T4CN remained unaltered by endothelium removal, as evidenced by the IC 50 values (108.35 [56.49-207.78] and 65.92 [39.72-109.40] µm, respectively). Pretreatment of endothelium-intact preparations with L-NAME, ODQ, glibenclamide, or TEA did not change the vasorelaxant effect of T4CN. Under Ca 2+ -free conditions, T4CN significantly reduced the phasic contractions induced by caffeine or PHE, as well as the contractions due to exogenous CaCl 2 in aortic preparations stimulated with PHE (in the presence of verapamil). These results suggest that in rat aortic rings, T4CN induced vasorelaxation independently from the activation of soluble guanylate cyclase/cGMP pathway, an effect that may be related to the electrophilicity of the substituted chloro-nitrostyrene. This vasorelaxation seems to involve inhibition of both calcium influx from the extracellular milieu and calcium mobilization from intracellular stores mediated by IP 3 receptors and by ryanodine-sensitive Ca 2+ channels.
(© 2020 Société Française de Pharmacologie et de Thérapeutique.)
Databáze: MEDLINE
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