The Lignan (-)-Cubebin Inhibits Vascular Contraction and Induces Relaxation Via Nitric Oxide Activation in Isolated Rat Aorta

Authors

  • Marco Túlio Menezes Carvalho,

    1. Laboratorio de Função Endotelial – Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, SP, Brazil
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  • Karen Cristina Souza Rezende,

    1. Núcleo de Pesquisa em Ciências Exatas e Tecnológicas da Universidade de Franca, Parque Universitário, Franca, SP, Brazil
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  • Paulo Roberto Barbosa Evora,

    1. Laboratorio de Função Endotelial – Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, SP, Brazil
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  • Jairo Kenupp Bastos,

    1. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
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  • Wilson Roberto Cunha,

    1. Núcleo de Pesquisa em Ciências Exatas e Tecnológicas da Universidade de Franca, Parque Universitário, Franca, SP, Brazil
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  • Marcio Luis Andrade e Silva,

    1. Núcleo de Pesquisa em Ciências Exatas e Tecnológicas da Universidade de Franca, Parque Universitário, Franca, SP, Brazil
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  • Andréa Carla Celotto

    Corresponding author
    1. Laboratorio de Função Endotelial – Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, SP, Brazil
    • Correspondence to: Dra. Andréa Carla Celotto, Av. Bandeirantes, 3900, 14.049-900 - HC-FMRP, 9o. andar, Ribeirão Preto, SP, Brazil.

      E-mail: acarla_c@yahoo.com

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Abstract

Cubebin, the most abundant lignan in Piper cubeba, has been described as having several effects as trypanocidal, antimycobacterial, antispasmodic, antimicrobial, anti-inflammatory, and analgesic. This study investigated the vasorelaxant effect produced by (-)-cubebin in isolated rat aortic rings pre-contracted with phenylephrine (Phe), and the possible mechanism involved in this event was evaluated. Endothelium-dependent relaxation was evoked by acetylcholine and (-)-cubebin in intact aortic rings, while endothelium-independent vasorelaxation was elicited by sodium nitroprusside and (-)-cubebin in denuded rings. Cumulative concentration–response curves for Phe (10−10–10−5 M) were determined for endothelium-intact and endothelium-denuded aortic rings in either the presence or absence of (-)-cubebin. Dose–response curves were also constructed for pre-incubation of vascular rings with Nω-nitro-L-arginine methyl ester (L-NAME) (a non-specific nitric oxide synthase inhibitor), indomethacin (an unspecific cyclooxygenase inhibitor), and 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) (a guanylyl cyclase inhibitor). (-)-Cubebin was found to exert a vasorelaxant effect irrespective of the presence of endothelium, which was abolished by pretreatment with L-NAME and ODQ, but not with indomethacin. In addition, (-)-cubebin was able to reduce Phe contraction in the case of intact rings. These results suggest that (-)-cubebin promotes vasorelaxation via NO/cGMP pathway in rat aorta, without prostacyclin involvement. Copyright © 2013 John Wiley & Sons, Ltd.

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