Potassium Channels‐Mediated Vasorelaxation of Rat Aorta Induced by Resveratrol

Novakovic, Aleksandra; Bukarica, Ljiljana Gojković; Kanjuh, Vladimir; Heinle, H.

doi:10.1111/j.1742-7843.2006.pto_531.x

Cited by 66 publications

(67 citation statements)

References 31 publications

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“…115 Resveratrol induced concentration-dependent relaxation of rat aortic rings with and without endothelium and margatoxin-sensitive K(+) channels located in the smooth muscle of rat aorta mediated this relaxation effect. 116 The same group repeated the study using endothelium-independent human internal mammary artery (HIMA) obtained from male patients undergoing coronary artery bypass surgery, and a similar conclusion was reached. 117 Resveratrol also inhibits the production of endogenous vasoconstrictors.…”

Section: Effect On Vasorelaxationmentioning

confidence: 71%

Resveratrol: A multitargeted agent for age-associated chronic diseases

Harikumar¹,

Aggarwal²

2008

Cell Cycle

484

339

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Extensive research within the last decade has revealed that most chronic illnesses such as cancer, cardiovascular and pulmonary diseases, neurological diseases, diabetes, and autoimmune diseases exhibit dysregulation of multiple cell signaling pathways that have been linked to inflammation. Thus mono-targeted therapies developed for the last two decades for these diseases have proven to be unsafe, ineffective and expensive. Although fruits and vegetables are regarded to have therapeutic potential against chronic illnesses, neither their active component nor the mechanism of action is well understood. Resveratrol (trans-3, 5, 4'-trihydroxystilbene), a component of grapes, berries, peanuts and other traditional medicines, is one such polyphenol that has been shown to mediate its effects through modulation of many different pathways. This stilbene has been shown to bind to numerous cell-signaling molecules such as multi drug resistance protein, topoisomerase II, aromatase, DNA polymerase, estrogen receptors, tubulin and F1-ATPase. Resveratrol has also been shown to activate various transcription factor (e.g., NFκB, STAT3, HIF-1α, β-catenin and PPAR-γ), suppress the expression of antiapoptotic gene products (e.g., Bcl-2, Bcl-X L , XIAP and survivin), inhibit protein kinases (e.g., src, PI3K, JNK and AKT), induce antioxidant enzymes (e.g., catalase, superoxide dismutase and hemoxygenase-1), suppress the expression of inflammatory biomarkers (e.g., TNF, COX-2, iNOS and CRP), inhibit the expression of angiogenic and metastatic gene products (e.g., MMPs, VEGF, cathepsin D and ICAM-1), and modulate cell cycle regulatory genes (e.g., p53, Rb, PTEN, cyclins and CDKs). Numerous animal studies have demonstrated that this polyphenol holds promise against numerous age-associated diseases including cancer, diabetes, Alzheimer, cardiovascular and pulmonary diseases. In view of these studies, resveratrol's prospects for use in the clinics are rapidly accelerating. Efforts are also underway to improve its activity in vivo through structural modification and reformulation. Our review describes various targets of resveratrol and their therapeutic potential.

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Section: Effect On Vasorelaxationmentioning

confidence: 71%

Resveratrol: A multitargeted agent for age-associated chronic diseases

Harikumar¹,

Aggarwal²

2008

Cell Cycle

484

339

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“…K V 1.1 and K V 1.6 channels were detected in smooth muscle cell of rat aorta and rat pulmonary artery, but not in smooth muscle cells of mesenteric artery (36,40). In prior experiments, we found that margatoxin abolished resveratrol-induced relaxation of human internal mammary artery and rat aorta (7,16). However, in the present study, margatoxin used in a concentration (10 nM) sufficient to block K V 1 channels did not change the resveratrol-induced relaxation, suggesting that K V 1 channels are not involved in the mechanism of resveratrol-induced endothelium-independent vasodilatation of rat mesenteric artery.…”

Section: Discussionmentioning

confidence: 99%

“…Also, in different experimental models, resveratrol can activate adenylate cyclase and membrane-bound guanylyl cyclase and inhibit cGMP-specific phosphodiesterse-5 (13 -15). Previously, we have shown that resveratrol produces relaxation of the isolated human internal mammary artery and rat aorta by activation of margatoxin-sensitive voltage-dependent K + (K V ) channels located in the smooth muscle (7,16). In contrast, Orsini et al (17) suggested that resveratrol derivates inhibited K V channels in the F-11 neuroblastoma cells.…”

Section: Introductionmentioning

confidence: 99%

A Role of Ion Channels in the Endothelium-Independent Relaxation of Rat Mesenteric Artery Induced by Resveratrol

et al. 2008

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Abstract.Recently it has been suggested that resveratrol relaxes different isolated arteries. The present study addressed the question whether different ion channels are involved in the endothelium-independent mechanism of vasodilatation induced by resveratrol. For that purpose, we tested the action of resveratrol on the rat mesenteric artery without endothelium. Resveratrol induced concentration-dependent relaxation of rat mesenteric artery. Among the K + -channel blockers, 4-amynopiridine (4-AP) moderately antagonized the resveratrol-induced relaxation, while glibenclamide, tetraethylammonium chloride, charybdotoxin, margatoxin, and barium chloride did not inhibit resveratrol-induced vasorelaxation. In rings, precontracted with 100 mM K + , the relaxant responses to resveratrol were highly significantly shifted to the right compared to those obtained in rings precontracted with phenylephrine, but resveratrol-induced maximal relaxation was only slightly affected. In order to minimize the influence of K + channels and voltage-gated Ca 2+ channels (VGCCs) in vascular smooth muscle, the third contraction was made by 100 mM K + in the presence of nifedipine. The relaxant response to resveratrol was abolished. Thus, the mechanism of vasorelaxation induced by resveratrol probably involves activation of 4-AP-sensitive K + channels. Its ability to completely relax the mesenteric artery precontracted with K + -rich solution suggests that K + channel-independent mechanism(s) are involved in its vasorelaxant effect. It seems that interaction with VGCCs plays a part in this K + channel-independent effect of resveratrol.

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“…Previous studies have found that Res relaxes many types of vascular beds without endothelium through the activation of different types of K + channels. The voltage-dependent K + channel plays an important role in the vasodilatation induced by Res in the aorta (6) and internal mammary artery (9), whereas, the voltage-dependent K + channel is involved in the vasodilatation induced by Res in the thoracic aorta (6). In addition, Res has been shown to induce relaxation of the abdominal aorta through activation of ATP-sensitive K + channels and Ca 2+ -activated K + channels (7).…”

Section: Discussionmentioning

confidence: 99%

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

Chen¹,

Xu²,

Wei

et al. 2016

Experimental and Therapeutic Medicine

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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.

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Potassium Channels‐Mediated Vasorelaxation of Rat Aorta Induced by Resveratrol

Cited by 66 publications

References 31 publications

Resveratrol: A multitargeted agent for age-associated chronic diseases

Resveratrol: A multitargeted agent for age-associated chronic diseases

A Role of Ion Channels in the Endothelium-Independent Relaxation of Rat Mesenteric Artery Induced by Resveratrol

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

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