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Molecules 2014, 19(5), 6863-6876; doi:10.3390/molecules19056863
Article

Calcium Influx Inhibition is Involved in the Hypotensive and Vasorelaxant Effects Induced by Yangambin

1,2, 3, 1, 4, 4, 1,2, 1,2, 5, 5, 4 and 1,2,*
1 Laboratório de Farmacologia Cardiovascular, Centro de Biotecnologia, Universidade Federal da Paraíba, Cidade Universitária, 58051-900 João Pessoa, PB, Brazil 2 Departamento de Ciências Farmacêutica, Centro de Ciências da Saúde, Universidade Federal da Paraíba, Cidade Universitária, 58051-900 João Pessoa, PB, Brazil 3 Laboratório de Neurociências, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Avenida Reitor Miguel Calmon, Vale do Canela, 40110-902 Salvador, BA, Brazil 4 Departamento de Fisiologia e Patologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba, Cidade Universitária, 58051-900 João Pessoa, PB, Brazil 5 Departamento de Farmacologia, Escola de Medicina de Ribeirão Preto, Universidade de São Paulo, postal code Ribeirão Preto, SP, Brazil
* Author to whom correspondence should be addressed.
Received: 27 February 2014 / Revised: 13 May 2014 / Accepted: 15 May 2014 / Published: 23 May 2014
(This article belongs to the Section Metabolites)
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Abstract

The pharmacological effects on the cardiovascular system of yangambin, a lignan isolated from Ocotea duckei Vattimo (Lauraceae), were studied in rats using combined functional and biochemical approaches. In non-anaesthetized rats, yangambin (1, 5, 10, 20, 30 mg/kg, i.v.) induced hypotension (−3.5 ± 0.2; −7.1 ± 0.8; −8.9 ± 1.3; −14 ± 2.3, −25.5% ± 2.6%, respectively) accompanied by tachycardia (5.9 ± 0.5; 5.9 ± 1.6; 8.8 ± 1.4; 11.6, 18.8% ± 3.4%, respectively). In isolated rat atria, yangambin (0.1 µM–1 mM) had very slight negative inotropic (Emax = 35.6% ± 6.4%) and chronotropic effects (Emax = 10.2% ± 2.9%). In endothelium-intact rat mesenteric artery, yangambin (0.1 µM–1 mM) induced concentration-dependent relaxation (pD2 = 4.5 ± 0.06) of contractions induced by phenylephrine and this effect was not affected by removal of the endothelium. Interestingly, like nifedipine, the relaxant effect induced by yangambin was more potent on the contractile response induced by KCl 80 mM (pD2 = 4.8 ± 0.05) when compared to that induced by phenylephrine. Furthermore, yangambin inhibited CaCl2-induced contractions in a concentration-dependent manner. This lignan also induced relaxation (pD2 = 4.0 ± 0.04) of isolated arteries pre-contracted with S(−)-Bay K 8644. In fura-2/AM-loaded myocytes of rat mesenteric arteries, yangambin inhibited the Ca2+ signal evoked by KCl 60 mM. In conclusion, these results suggest that the hypotensive effect of yangambin is probably due to a peripheral vasodilatation that involves, at least, the inhibition the Ca2+ influx through voltage-gated Ca2+ channels.
Keywords: lignan; yangambin; mesenteric artery; vasodilation; calcium influx lignan; yangambin; mesenteric artery; vasodilation; calcium influx
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Araújo, I.G.A.; Silva, D.F.; do Carmo de Alustau, M.; Dias, K.L.G.; Cavalcante, K.V.M.; Veras, R.C.; Barbosa-Filho, J.M.; Neto, M.A.; Bendhack, L.M.; de Azevedo Correia, N.; Almeida de Medeiros, I. Calcium Influx Inhibition is Involved in the Hypotensive and Vasorelaxant Effects Induced by Yangambin. Molecules 2014, 19, 6863-6876.

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