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The triterpenoid alpha, beta-amyrin prevents the impaired aortic vascular reactivity in high-fat diet-induced obese mice

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Abstract

To characterize the protective effects of the triterpenoid mixture alpha, beta-amyrin (AMY, 20 mg/kg, during 15 days) on the reactivity of isolated aorta of high-fat diet (HFD)-induced obese mice. Male Swiss mice were fed with HFD or normal diet (ND) for 15 weeks. Contractions of thoracic aorta in response to KCl or phenylephrine (PHE) and relaxation by acetylcholine (ACh) or sodium nitroprusside (SNP) were analyzed. HFD-fed mice developed hyperglycemia, hyperlipidemia, and significant body weight gain, parameters prevented by AMY treatment. Whereas aortic contractility did not differ in response to KCl, contractions induced by PHE (1 μM) as well as relaxation induced by ACh (1–30 μM) or SNP (1 nM–0.1 mM) on PHE-contracted aorta were decreased (p < 0.05) in tissues of HFD compared to ND mice, phenomenon significantly (p < 0.05) diminished in HFD mice treated with AMY. The relaxant actions of ACh and SNP were inhibited (p < 0.05) by tetraethylammonium (TEA, 5 mM), apamin (0.1 μM), and 4-aminopyridine (4-AP; 3 mM) in aortae from ND group, but not from HFD. Treatment of HFD mice with AMY rescued the inhibitory effect of TEA (p < 0.05) on vasorelaxant actions of ACh and SNP. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) inhibited similarly the relaxant effects of SNP in all groups. 8-Br-cGMP relaxed with similar profile aortae of all groups. By preventing HFD-induced obesity in mice, AMY rescued the blunted contractile response to PHE, and the attenuated vasorelaxation and K+ channel activation (opening) induced by ACh and SNP in isolated aorta.

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Abbreviations

Ach:

Acetylcholine

4-AP:

4-aminopyridine

AMY:

Alpha, beta-amyrin

ANOVA:

Analysis of variance

BKCa:

Large-conductance Ca2+-activated potassium channel

DMEM:

Dulbecco’s modified Eagle’s medium

DMSO:

Dimethyl sulfoxide

EDTA:

Ethylenediaminetetraacetic acid

ELISA:

Enzyme-linked immunosorbent assay

FBS:

Fetal bovine serum

GLIB:

Glibenclamide

HFD:

High-fat diet

KATP :

ATP-sensitive potassium channel

Kv:

Voltage-dependent potassium channel

MKHS:

Modified Krebs-Henseleit solution

ND:

Normal diet

NO:

Nitric oxide

ODQ:

1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one

PHE:

Phenylephrine

PSS:

Physiological salt solution

SD:

Standard deviation

SEM:

Standard error of mean

SK:

Small conductance Ca2+-activated potassium channel

SNP:

Sodium nitroprusside

TEA:

Tetraethylammonium

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Acknowledgements

This research was supported by the grants and fellowships from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP). We are grateful to Maria Aldiléia Rocha Morais for their excellent technical assistance.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, 60430-270, Brazil

    Flávia Almeida Santos, Karine Maria Martins Bezerra Carvalho, Francisco José Batista-Lima, Paulo Iury Gomes Nunes, Ana Flávia Seraine Custódio Viana, Vietla Satyanarayana Rao, Pedro Jorge Caldas Magalhães & Teresinha Silva de Brito

  2. Department of Organic Chemistry, Federal University of Piauí, Teresina, Piauí, Brazil

    Armenio André de Carvalho Almeida da Silva & Mariana Helena Chaves

  3. Faculty of Pharmacy, Odontology and Nursing, Federal University of Ceará, Fortaleza, Ceará, Brazil

    Said Gonçalves da Cruz Fonseca

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  1. Flávia Almeida Santos
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  2. Karine Maria Martins Bezerra Carvalho
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Correspondence to Flávia Almeida Santos.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution (Federal University of Ceará).

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Santos, F.A., Carvalho, K.M.M.B., Batista-Lima, F.J. et al. The triterpenoid alpha, beta-amyrin prevents the impaired aortic vascular reactivity in high-fat diet-induced obese mice. Naunyn-Schmiedeberg's Arch Pharmacol 390, 1029–1039 (2017). https://doi.org/10.1007/s00210-017-1404-1

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