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. 2011 May 15;589(Pt 10):2585-96.
doi: 10.1113/jphysiol.2011.206078. Epub 2011 Mar 14.

Dehydroepiandrosterone protects against oxidative stress-induced endothelial dysfunction in ovariectomized rats

João Paulo Gabriel Camporez  1 , Eliana Hiromi Akamine, Ana Paula Davel, Celso Rodrigues Franci, Luciana Venturini Rossoni, Carla Roberta de Oliveira Carvalho
Affiliations

Dehydroepiandrosterone protects against oxidative stress-induced endothelial dysfunction in ovariectomized rats

João Paulo Gabriel Camporez et al. J Physiol. .

Abstract

Cardiovascular disease is less frequent in premenopausal women than in age-matched men or postmenopausal women. Moreover, the marked age-related decline in serum dehydroepiandrosterone (DHEA) level has been associated to cardiovascular disease. The aim of this study was to evaluate the effects of DHEA treatment on vascular function in ovariectomized rats. At 8 weeks of age, female Wistar rats were ovariectomized (OVX) or sham (SHAM) operated and 8 weeks after surgery both groups were treated with vehicle or DHEA (10mg kg⁻¹ week⁻¹) for 3 weeks. Aortic rings were used to evaluate the vasoconstrictor response to phenylephrine (PHE) and the relaxation responses to acetylcholine (ACh) and sodium nitroprusside (SNP). Tissue reactive oxygen species (ROS) production and SOD, NADPH oxidase and eNOS protein expression were analysed. PHE-induced contraction was increased in aortic rings from OVX compared to SHAM, associated with a reduction in NO bioavailability. Furthermore, the relaxation induced by ACh was reduced in arteries from OVX, while SNP relaxation did not change. The incubation of aortic rings with SOD or apocynin restored the enhanced PHE-contraction and the impaired ACh-relaxation only in OVX. DHEA treatment corrected the increased PHE contraction and the impaired ACh-induced relaxation observed in OVX by an increment in NO bioavailability and decrease in ROS production. Besides, DHEA treatment restores the reduced Cu/Zn-SOD protein expression and eNOS phosphorylation and the increased NADPH oxidase protein expression in the aorta of OVX rats. The present results suggest an important action of DHEA, improving endothelial function in OVX rats by acting as an antioxidant and enhancing the NO bioavailability.

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Figures

Figure 1
Figure 1. Vascular reactivity to phenylephrine, acetylcholine and sodium nitroprusside
Concentration–response curve to phenylephrine (A), acetylcholine (B) and sodium nitroprusside (C) in endothelium-intact aortic rings from SHAM, OVX and DHEA-treated rats. Results are expressed as means ± SEM. Two-way ANOVA: *P < 0.01 in comparison to SHAM (n = 9–13).
Figure 2
Figure 2. Reactive oxygen species in aorta
Representative fluorescence photomicrographs of microscopic sections of thoracic aorta from SHAM, OVX and DHEA-treated rats. Vessels were labelled with the oxidative dye hydroethidine, which produces a red fluorescence when oxidized to ethidium bromide by superoxide anion. Quantitative analysis for fluorescence photomicrographs of microscopic sections of thoracic aorta from SHAM, OVX and DHEA-treated rats. Results are expressed as means ± SEM. Two-way ANOVA: *P < 0.01 in comparison to SHAM and #P < 0.01 in comparison to OVX (n = 7).
Figure 3
Figure 3. eNOS protein expression and phosphorylation in aorta
Representative Western blots (top) and quantitative analysis (bottom) for total eNOS protein expression (A) and ser1177 eNOS phosphorylation (B) in thoracic aorta from SHAM, OVX and DHEA-treated rats. Results are expressed as means ± SEM. Two-way ANOVA: *P < 0.01 in comparison to SHAM and #P < 0.01 in comparison to OVX (n = 9).
Figure 4
Figure 4. Cu/Zn-SOD and Mn-SOD protein expression in aorta
Representative Western blots (top) and quantitative analysis (bottom) for Cu/Zn-SOD (A) and Mn-SOD (B) protein expression in thoracic aorta from SHAM, OVX and DHEA-treated rats. Results are expressed as means ± SEM. Two-way ANOVA: *P < 0.01 in comparison to SHAM and #P < 0.01 in comparison to OVX (n = 8).
Figure 5
Figure 5. NADPH oxidase subunits protein expression in aorta
Representative Western blots (top) and quantitative analysis (bottom) for gp91phox (A) and p22phox (B) protein expression in thoracic aorta from SHAM, OVX and DHEA-treated rats. Results are expressed as means ± SEM. Two-way ANOVA: *P < 0.01 in comparison to SHAM and #P < 0.01 in comparison to OVX (n = 8).
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References

    1. Aragno M, Mastrocola R, Alloatti G, Vercellinatto I, Bardini P, Geuna S, Catalano MG, Danni O, Boccuzzi G. Oxidative stress triggers cardiac fibrosis in the heart of diabetic rats. Endocrinology. 2008;149:380–388. - PubMed
    1. Aragno M, Mastrocola R, Catalano MG, Brignardello E, Danni O, Boccuzzi G. Oxidative stress impairs skeletal muscle repair in diabetic rats. Diabetes. 2004;53:1082–1088. - PubMed
    1. Aragno M, Mastrocola R, Medana C, Graziella M, Vercellinatto I, Danni O, Boccuzzi G. Oxidative stress-dependent impairment of cardiac-specific transcription factors in experimental diabetes. Endocrinology. 2006;147:5967–5974. - PubMed
    1. Aragno M, Tamagno E, Gatto V, Brignardello E, Parola S, Danni O, Boccuzzi G. Dehydroepiandrosterone protects tissues of streptozotocin-treated rats against oxidative stress. Free Radic Biol Med. 1999;26:1467–1474. - PubMed
    1. Barrett-Connor E, Khaw KT, Yen S. A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. N Engl J Med. 1986;315:1519–1524. - PubMed

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