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. 2017 Jun 29;109(2):0.
doi: 10.5935/abc.20170090. Online ahead of print.

Ruthenium Complex Improves the Endothelial Function in Aortic Rings From Hypertensive Rats

[Article in English, Portuguese]
Izabela Pereira Vatanabe  1 , Carla Nascimento Dos Santos Rodrigues  1 , Tereza Cristina Buzinari  1 , Thiago Francisco de Moraes  1 , Roberto Santana da Silva  2 , Gerson Jhonatan Rodrigues  1
Affiliations

Ruthenium Complex Improves the Endothelial Function in Aortic Rings From Hypertensive Rats

[Article in English, Portuguese]
Izabela Pereira Vatanabe et al. Arq Bras Cardiol. .

Abstract

Background:: The endothelium is a monolayer of cells that extends on the vascular inner surface, responsible for the modulation of vascular tone. By means of the release of nitric oxide (NO), the endothelium has an important protective function against cardiovascular diseases.

Objective:: Verify if cis- [Ru(bpy)2(NO2)(NO)](PF6)2 (BPY) improves endothelial function and the sensibility of conductance (aorta) and resistance (coronary) to vascular relaxation induced by BPY.

Methods:: Normotensive (2K) and hypertensive (2K-1C) Wistar rats were used. For vascular reactivity study, thoracic aortas were isolated, rings with intact endothelium were incubated with: BPY(0.01 to10 µM) and concentration effect curves to acetylcholine were performed. In addition, cumulative concentration curves were performed to BPY (1.0 nM to 0.1 µM) in aortic and coronary rings, with intact and denuded endothelium.

Results:: In aorta from 2K-1C animals, the treatment with BPY 0.1µM increased the potency of acetylcholine-induced relaxation and it was able to revert the endothelial dysfunction. The presence of the endothelium did not modify the effect of BPY in inducing the relaxation in aortas from 2K and 2K-1C rats. In coronary, the endothelium potentiated the vasodilator effect of BPY in vessels from 2K and 2K-1C rats.

Conclusion:: Our results suggest that 0.1 µM of BPY is able to normalize the relaxation endothelium dependent in hypertensive rats, and the compound BPY induces relaxation in aortic from normotensive and hypertensive rats with the same potency. The endothelium potentiate the relaxation effect induced by BPY in coronary from normotensive and hypertensive rats, with lower effect on coronary from hypertensive rats.

Fundamento:: O endotélio é uma monocamada de células que se estende sobre a superfície interna vascular, responsável pela modulação do tônus vascular. Por meio da liberação de óxido nítrico (NO), o endotélio tem uma função protetora importante contra doenças cardiovasculares.

Objetivo:: Verificar se o cis- [Ru (BPY)2 (NO2) (NO)] (PF6) 2 (BPY) melhora a função endotelial e a sensibilidade da condutância (aorta) e da resistência (coronária) ao relaxamento vascular induzido por BPY.

Métodos:: Foram utilizados ratos Wistar normotensos (2K) e hipertensos (2K-1C). Para o estudo de reatividade vascular, as aortas torácicas foram isoladas, os anéis com endotélio intacto foram incubados com: BPY (0,01 a 10 µM) e se realizaram curvas de efeito de concentração para acetilcolina. Adicionalmente, foram feitas curvas de concentração cumulativas para BPY (1,0 nM a 0,1 µM) nos anéis aórticos e coronários, com endotélio intacto e nu.

Resultados:: Na aorta de animais 2K-1C, o tratamento com BPY 0,1 µM aumentou a potência do relaxamento induzido pela acetilcolina e foi capaz de reverter a disfunção endotelial. A presença do endotélio não modificou o efeito da BPY na indução do relaxamento em aortas de ratos 2K e 2K-1C. Na coronária, o endotélio potencializou o efeito vasodilatador do BPY em vasos de ratos 2K e 2K-1C.

Conclusão:: Nossos resultados sugerem que 0,1 µM de BPY é capaz de normalizar o relaxamento dependente do endotélio em ratos hipertensos, e o composto BPY induz relaxamento na aorta de ratos normotensos e hipertensos com a mesma potência. O endotélio potencializa o efeito de relaxamento induzido pela BPY em coronárias de ratos normotensos e hipertensos, com menor efeito em coronárias de ratos hipertensos.

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Conflict of interest statement

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Figures

Figure 1
Figure 1
Concentration-response curves (n = 8) for acetylcholine in intact endothelium- aortic rings contracted with phenylephrine. Values are mean ± S.D of experiments performed on preparations obtained from different animals. *** indicates signifcant difference (p < 0.001) in pD2 value for 2K vs. 2K-1C.
Figure 2
Figure 2
Concentration-response curves for acetylcholine (BPY) in aortic rings with intact endothelium and incubated with different concentrations of cis-[Ru(bpy)2(NO2-) (NO)](PF6)2 and contracted with phenylephrine. Values are mean ± S.D of experiments performed on preparations obtained from different animals.* indicates signifcant difference 2K-1C PBS vs 2K-1C BPY 0.1 µM (p < 0.001) e 2K-1C PBS vs 2K PBS (p < 0.001) in pD2.
Figure 3
Figure 3
Presents differences in the potency (pD2) of acetylcholine in inducing relaxation in aortas with and without cis-[Ru(bpy)2(NO2-)(NO)](PF6)2 treatment. The concentration 0.1 nM normalized relaxation in 2K-1C aortic rings compared to 2K aortic rings. *** - Indicates statistical difference between 2K-1C PBS vs. 2K-1C BPY 0.1 µM (p < 0.001) and 2K-1C PBS vs. 2K PBS (p < 0.001).
Figure 4
Figure 4
Presents differences in the effciency (Emax) of acetylcholine in inducing relaxation in aortas with and without cis-[Ru(bpy)2(NO2-)(NO)](PF6)2 treatment. The concentration 0.1 nM normalized relaxation in 2K-1C aortic rings compared to 2K aortic rings. *** - Indicates statistical difference between 2K-1C PBS vs. 2K-1C BPY 0.1 µM (p < 0.001) and 2K-1C PBS vs. 2K PBS (p < 0.001).
Figure 5
Figure 5
Concentration-response curves for acetylcholine in aortic rings with (E+) and without (E-) intact endothelium, from rats 2K and 2K-1C and incubated with different concentrations of cis-[Ru(bpy)2(NO2 -)(NO)](PF6)2 and contracted with phenylephrine. Values are mean ± S.D of experiments performed on preparations obtained from different animals. There was no statistical difference.
Figure 6
Figure 6
Relaxation coronary artery of rats (2K-1C) with (E +) and without (E-) form endothelium induced by compound cis-[Ru(bpy)2(NO2 -)(NO)](PF6)2 in rings pre-contracted with serotonin (SE). Curves cumulative concentration-effect were performed for BPY compound. Each point represents the mean ± S.D of data obtained from 5-7 independent determinations. * Indicates difference in the value of Emax.
Figure 7
Figure 7
Coronary artery relaxation of normotensive rats (2K) with (E +) and without (E-) form endothelium induced by compound cis-[Ru(bpy)2(NO2-)(NO)](PF6)2, in coronary rings contracted with serotonin. Curves cumulative concentration-effect were performed for BPY compound. Each point represents the mean ± S.D of data obtained in fve independent determinations. *Indicates difference in the value of Emax.
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