Ellagic Acid‐Induced Endothelium‐Dependent and Endothelium‐Independent Vasorelaxation in Rat Thoracic Aortic Rings and the Underlying Mechanism

Yılmaz, Bedriniam; Usta, Coşkun

doi:10.1002/ptr.4716

Cited by 35 publications

(17 citation statements)

References 25 publications

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“…Thus, our results are in agreement with literature data, since the endothelium-dependent relaxation was enhanced in all treated groups (Machha and Mustafa, 2005; Ajay et al, 2007; Yilmaz and Usta, 2013). Nevertheless, L-NAME impaired the endothelium-dependent relaxation, which shows that there is a strong participation of NO in this response.…”

Section: Discussionsupporting

confidence: 93%

Pomegranate Extract Enhances Endothelium-Dependent Coronary Relaxation in Isolated Perfused Hearts from Spontaneously Hypertensive Ovariectomized Rats

et al. 2017

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Decline in estrogen levels promotes endothelial dysfunction and, consequently, the most prevalent cardiovascular diseases in menopausal women. The use of natural therapies such as pomegranate can change these results. Pomegranate [Punica granatum L. (Punicaceae)] is widely used as a phytotherapeutic agent worldwide, including in Brazil. We hypothesized that treatment with pomegranate hydroalcoholic extract (PHE) would improve coronary vascular reactivity and cardiovascular parameters. At the beginning of treatment, spontaneously hypertensive female rats were divided into Sham and ovariectomized (OVX) groups, which received pomegranate extract (PHE) (250 mg/kg) or filtered water (V) for 30 days by gavage. Systolic blood pressure was measured by tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed by Langendorff retrograde perfusion technique. A dose-response curve for bradykinin was performed, followed by L-NAME inhibition. The protein expression of p-eNOS Ser1177, p-eNOS Thr495, total eNOS, p-AKT Ser473, total AKT, SOD-2, and catalase was quantified by Western blotting. The detection of coronary superoxide was performed using the protocol of dihydroethidium (DHE) staining Plasma nitrite measurement was analyzed by Griess method. Systolic blood pressure increased in both Sham-V and OVX-V groups, whereas it was reduced after treatment in Sham-PHE and OVX-PHE groups. The baseline coronary perfusion pressure was reduced in the Sham-PHE group. The relaxation was significantly higher in the treated group, and L-NAME attenuated the relaxation in all groups. The treatment has not changed p-eNOS (Ser1177), total eNOS, p-AKT (Ser473) and total AKT in any groups. However, in Sham and OVX group the treatment reduced the p-eNOS (Thr495) and SOD-2. The ovariectomy promoted an increasing in the superoxide anion levels and the treatment was able to prevent this elevation and reducing oxidative stress. Moreover, the treatment prevented the decreasing in plasmatic nitrite. We observed a reduction in total cholesterol and LDL in the Sham-PHE group. The treatment with PHE enhances the endothelium-dependent coronary relaxation and improves cardiovascular parameters, which suggests a therapeutic role of PHE.

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Section: Discussionsupporting

confidence: 93%

Pomegranate Extract Enhances Endothelium-Dependent Coronary Relaxation in Isolated Perfused Hearts from Spontaneously Hypertensive Ovariectomized Rats

et al. 2017

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“…Aortas were incubated with 30 mM HG for 24 hours in the presence or absence of 20 uM EA. Concentration of EA was chosen based on previous published reports [31][32][33]. 5 mM normal glucose (NG) was used as control.…”

Section: Organ Culture Of Isolated Aortasmentioning

confidence: 99%

Ellagic Acid Reduces High Glucose-Induced Vascular Oxidative Stress Through ERK1/2/NOX4 Signaling Pathway

Rozentsvit

Vinokur

Samuel

et al. 2017

Cell Physiol Biochem

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Background/Aims: Elevated production of reactive oxygen species (ROS) is linked to endothelial dysfunction and is one of the key contributors to the pathogenesis of diabetic vascular complications. Emerging evidence has indicated that ellagic acid (EA), a polyphenol found in fruits and nuts, possesses numerous biological activities including radical scavenging. However, whether EA exerts a vasculo-protective effect via antioxidant mechanisms in blood vessels exposed to diabetic conditions remains unknown. Accordingly, the goal of this current study was to determine whether EA decreases vascular ROS production and thus ameliorates endothelial dysfunction in the diabetic milieu. Methods: Intact rat aortas and human aortic endothelial cells (HAEC) were stimulated with 30mM high glucose (HG) with and without EA co-treatment. Endothelium-dependent vasodilation was measured using a wire myograph. Gene and protein expression of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 4 (NOX4) were detected using RT-PCR and western blotting, respectively. Oxidative stress was determined by measuring ROS levels using dihydroethidium (DHE) staining. Results: Intact aortas exposed to HG condition displayed exacerbated ROS production and impairment of endothelium-dependent vasodilation, characterizing endothelial dysfunction. These effects were markedly reduced with EA treatment. HG enhanced ROS production in HAEC, paralleled by increased ERK1/2 activation and NOX4 expression. EA treatment blunted the increase of ROS generation, ERK1/2 activation and decreased NOX4. Conclusions: EA significantly decreases endothelial ROS levels and ameliorates the impairment of vascular relaxation induced by HG. Our results suggest that EA exerts a vasculo-protective effect under diabetic conditions via an antioxidant effect that involves inhibition of ERK1/2 and downregulation of NOX4.

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“…P values lower than 0.05 were considered significant. In all experiments, n equals the number of rats from which vessel segment were obtained (26).…”

Section: Discussionmentioning

confidence: 99%

“…Once a stable contraction was achieved, PSO (10 -8 -10 -4 M) was added cumulatively on aortic rings with or without endothelium into organ bath. To characterize the mechanisms involved in PSO-induced vasorelaxant effect, the aortic rings were incubated with each inhibitor added to the bath for 30 min before PE was added to increase tone (26).…”

Section: Experimental Protocolmentioning

confidence: 99%

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Punicic Acid Induces Endothelium-Dependent Vasorelaxation in Rat Thoracic Aortic Rings

Yılmaz¹,

Usta²,

Taşatargil³

et al. 2015

Akd Med J

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Objective: The aim of the present study was to investigate the possible mechanism by which pomegranate seed oil causes vasodilatation in isolated thoracic aorta rings form the rat. Material and Methods: The isolated rat arteries were cut into rings and placed in tissue chambers filled with Krebs solution. results: Pomegranate seed oil produced a concentration-dependent relaxation in rings with endothelium. However, it didn't cause any relaxant effect in the absence of endothelium. L-NAME and ODQ produced a significant inhibition in the rings with endothelium. Subsequent addition of L-arginine reversed the inhibitory effects of L-NAME. However, the relaxant effect of PSO did not change with tetraethylammonium, 4-aminopyridine and glibenclamide, in rings either with or without endothelium. Additionally, the relaxant effect of PSO was not affected by indomethacin, propranolol, losartan or captopril incubation. In another set of experiments rats were anaesthetised and surgically equipped with intraperitoneal radio-transmitters to record blood pressure in vivo. PSO caused a slight decrease in systolic and diastolic blood pressure along with mildly decreased heart rate. conclusion: These comprehensive findings clearly indicate that vasorelaxation is induced by PSO via modulation of nitric oxide-guanylyl cyclase pathway.

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Ellagic Acid‐Induced Endothelium‐Dependent and Endothelium‐Independent Vasorelaxation in Rat Thoracic Aortic Rings and the Underlying Mechanism

Cited by 35 publications

References 25 publications

Pomegranate Extract Enhances Endothelium-Dependent Coronary Relaxation in Isolated Perfused Hearts from Spontaneously Hypertensive Ovariectomized Rats

Pomegranate Extract Enhances Endothelium-Dependent Coronary Relaxation in Isolated Perfused Hearts from Spontaneously Hypertensive Ovariectomized Rats

Ellagic Acid Reduces High Glucose-Induced Vascular Oxidative Stress Through ERK1/2/NOX4 Signaling Pathway

Punicic Acid Induces Endothelium-Dependent Vasorelaxation in Rat Thoracic Aortic Rings

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