The effect of long-term resveratrol treatment on relaxation to estrogen in aortae from male and female rats: Role of nitric oxide and superoxide

Söylemez, Sibel; Gürdal, Hakan; Sepici, Aylin; Akar, Fatma

doi:10.1016/j.vph.2008.06.006

Cited by 28 publications

(45 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This suggests that nitric oxide (NO) is involved in the relaxation of Res in the superior mesenteric artery with endothelium, whereas the cGMP pathway and prostanoids are not associated with this effect. This finding is consistent with previous studies; in the abdominal aorta, thoracic aorta and coronary artery, the efficacy of Res has been found to be closely associated with the NO system in endothelial cells (4,7,8,12).…”

Section: Discussionsupporting

confidence: 93%

Endothelium-dependent and-independent relaxation induced by resveratrol in rat superior mesenteric arteries

Chen¹,

Xu²,

Wei

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Resveratrol (Res) is a specific agonist of sirtuin 1, and has many cardioprotective effects. Although Res is able to relax various vascular beds, its pharmacological properties in rat superior mesenteric arteries and the underlying mechanism are not well clarified. The aim of present study was to investigate the vasorelaxant effects of Res on rat superior mesenteric arteries and the mechanisms involved. The isometric tension of rat superior mesenteric arterial rings was recorded in vitro using myography. It was found that Res concentration-dependently relaxed endothelium-intact superior mesenteric artery rings pre-contracted by phenylephrine hydrochloride (E max , 97.66±0.79%; pD 2 , 4.30±0.14) or KCl (E max , 101.3±0.6%; pD 2 , 4.12±0.03). The vasorelaxant effect of Res on the superior mesenteric artery rings was partially endothelium-dependent. N G -nitro-L-arginine methyl ester (100 µM) significantly inhibited the Res-induced vasorelaxant effect. However, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (10 µM) and indomethacin (5 µM) each had no effect on the Res-induced vasorelaxation. In artery rings without endothelium, the vasorelaxation induced by Res was attenuated by 4-aminopyridine (100 µM) and glibenclamide (10 µM). However, barium chloride dehydrate (10 µM) and tetraethylammonium chloride (1 mM) did not affect the vasorelaxation induced by Res. Moreover, Res also inhibited the contraction induced by an increase in external calcium concentration in Ca 2+ -free medium plus KCl (60 mM). These results suggest that Res induces relaxation in superior mesenteric arterial rings through an endothelium-dependent pathway, involving nitric oxide release, and also through an endothelium-independent pathway, with opening of voltage-dependent K + channels and ATP-sensitive K + channels and blockade of extracellular Ca 2+ influx.

show abstract

Section: Discussionsupporting

confidence: 93%

Endothelium-dependent and-independent relaxation induced by resveratrol in rat superior mesenteric arteries

Chen¹,

Xu²,

Wei

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…The estrogenic properties of Resv have been reported but have not yet been well studied in the vasculature. In some prior reports, Resv induced aortic vasorelaxation via an ER-dependent mechanism (38). In vitro studies demonstrated that ICI-182780, a nonselective ER antagonist, blocks Resv-induced MAPK activity in endothelial cells (21).…”

Section: Discussionmentioning

confidence: 90%

Essential role of ER-α-dependent NO production in resveratrol-mediated inhibition of restenosis

Khandelwal

Hebert

Dugas

2010

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

veratrol (Resv), a red wine polyphenol, is known to exhibit vascular protective effects and reduce vascular smooth muscle cell mitogenesis. Vascular smooth muscle cell proliferation is a critical factor in the pathogenesis of restenosis, the renarrowing of vessels that often occurs after angioplasty and/or stent implantation. Although Resv has been shown to be an estrogen receptor (ER) modulator, the role of the ER in Resv-mediated protection against restenosis has not yet been elucidated in vivo. Therefore, with the use of a mouse carotid artery injury model, our objective was to determine the role of ER in modulating Resv-mediated effects on neointimal hyperplasia. Female wild-type and ER-␣ Ϫ/Ϫ mice were administered a high-fat diet Ϯ Resv for 2 wk. A carotid artery endothelial denudation procedure was conducted, and the mice were administered a high-fat diet Ϯ Resv for an additional 2 wk. Resv-treated wild-type mice exhibited a dramatic decrease in restenosis, with an increased arterial nitric oxide (NO) synthase (NOS) activity and NO production. However, in the ER-␣ Ϫ/Ϫ mice, Resv failed to afford protection and failed to increase NO production, apparently because of a decreased availability of the NOS cofactor tetrahydrobiopterin. To verify the role of NO in Resvmediated effects, mice were coadministered Resv plus a nonselective NOS inhibitor, N G -nitro-L-arginine methyl ester (L-NAME). Cotreatment with L-NAME significantly attenuated the antirestenotic properties of Resv. These data thus suggest that Resv inhibits vascular proliferative responses after injury, predominately through an ER-␣-dependent increase in NO production. estrogen receptor; nitric oxide RESTENOSIS, or vessel renarrowing, is a major limiting factor in patients undergoing angioplasty and/or stent implantation (25). The primary cause for restenosis is neointimal formation, characterized by abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) from the media of the vessel wall to the intima (32). Thus the inhibition of VSMC proliferation can potentially inhibit restenosis. Several clinical studies have demonstrated an increased risk for developing cardiovascular disorders in postmenopausal compared with premenopausal women (29). This suggests an important role for estrogen and estrogen receptors (ERs) in the increased incidence of cardiovascular disorders in postmenopausal women. Several rodent studies have assessed the efficacy of 17␤-estradiol, a synthetic estrogen, in inhibiting restenosis. A mechanism by which the ERs modulate vascular function is via an ER-dependent increase in nitric oxide (NO) synthase (NOS) activity and NO production, occurring through both genomic and nongenomic mechanisms (2,8,26).According to the French paradox, epidemiological evidence demonstrating a decreased incidence in cardiovascular disorders among French populations consuming high amounts of saturated fat was associated with a daily consumption of red wine. Resveratrol (Resv) is a red wine polyphenol believed to be a key contribut...

show abstract

“…Em aortas de ratos, a suplementação com resveratrol (50 mg /L na água de beber durante 21 dias) provocou inibição da NADPH-oxidase e diminuição na produção de superóxido (Soylemez et al, 2008;. Associada à atividade scavenger, polifenóis podem quelar metais, como ferro e cobre, e assim inibir a formação de radicais livres por meio da reação de Haber-Weiss/Fenton (Rodrigo et al, 2011).…”

Section: Mecanismos Moleculares De Ação De Polifenóis De Uvas E Vinhounclassified

Mecanismos moleculares de ação anti-inflamatória e antioxidante de polifenóis de uvas e vinho tinto na aterosclerose

Séfora-Sousa

Angelis-Pereira

2013

Rev. bras. plantas med.

View full text Add to dashboard Cite

RESUMO:Este trabalho visa investigar os possíveis mecanismos moleculares de ação dos polifenóis de uvas e vinho tinto contra os processos oxidativos e inflamatórios envolvidos na aterosclerose. Trata-se de um estudo de revisão de literatura realizado por meio de buscas nas bases de dados PubMed e ScienceDirect utilizando os seguintes descritores: vinho tinto, uva, polifenóis, resveratrol, aterosclerose, LDL-oxidada, inflamação, estresse oxidativo, NF-kB, AP-1, Nrf2, SIRT-1, MicroRNA. Embora tais mecanismos ainda não estejam totalmente esclarecidos, os estudos indicam que compostos fenólicos presentes em uvas podem se complexar com metais (como ferro e cobre) que provocam peroxidação dos lipídios, aumentam a atividade antioxidante do plasma, associam-se com a LDL-c aumentando sua resistência à oxidação, preservam a atividade da enzima paraoxonase, neutralizam radicais livres, e ativam fatores de transcrição como o Nrf2, que aumenta a expressão de genes que codificam proteínas importantes na defesa antioxidante, como a superóxido dismutase e a glutationa peroxidase. Além disso, os polifenóis inibem a fosforilação de MAP quinases, inibindo assim os fatores de transcrição NF-kB e AP-1 e, consequentemente, reduzindo a síntese do TNF-á, interleucinas, moléculas de adesão e quimiocinas. Também inibem a atividade das enzimas cicloxigenase e lipoxigenase. Outro mecanismo proposto é a ação do resveratrol sobre a atividade de deacetilases de histonas, como a SITR-1. Estas ações em conjunto reduzem a oxidação da LDL-c e o processo inflamatório, atenuando o processo aterogênico. Palavras-chave:Resveratrol, LDL-c, Nrf2, NF-kB, AP-1, aterosclerose.ABSTRACT: Molecular mechanisms of action of grape and red wine polyphenols against oxidative and inflammatory processes in atherosclerosis. This study aimed to investigate the possible molecular mechanisms of action of grape and red wine polyphenols against oxidative and inflammatory processes in atherosclerosis. This is a literature review performed by searching in the PubMed and ScienceDirect databases using the following descriptors: red wine, grape, polyphenols, resveratrol, atherosclerosis, oxidized LDL, inflammation, oxidative stress, NF-kB, AP-1, Nrf2, SIRT-1, MicroRNA. Although the mechanisms are not fully understood, studies indicate that phenolic compounds possibly complex with metals (such as iron and copper), or else they increase the antioxidant activity of plasma and also preserve the activity of enzyme paraoxonase. Moreover, the polyphenols neutralize free radicals and activate transcription factors, for example Nrf2, which increases the expression of genes that encode important proteins in antioxidant defense (such as superoxide dismutase and glutathione peroxidase). Additionally, polyphenols inhibit the phosphorylation of MAP kinases, causing a blocking effect on the transcription factors NF-kB and AP-1 and, consequently, blocking the synthesis of TNF-α, interleukins, chemokines and molecules adhesion. Moreover, it can inhibit the activity of the cycloxygenase and li...

show abstract

The effect of long-term resveratrol treatment on relaxation to estrogen in aortae from male and female rats: Role of nitric oxide and superoxide

Cited by 28 publications

References 32 publications

Endothelium-dependent and-independent relaxation induced by resveratrol in rat superior mesenteric arteries

Endothelium-dependent and-independent relaxation induced by resveratrol in rat superior mesenteric arteries

Essential role of ER-α-dependent NO production in resveratrol-mediated inhibition of restenosis

Mecanismos moleculares de ação anti-inflamatória e antioxidante de polifenóis de uvas e vinho tinto na aterosclerose

Contact Info

Product

Resources

About