Short-term exposure of erythropoietin impairs endothelial function through inhibition of nitric oxide production and eNOS mRNA expression in the rat pulmonary artery

Sultan, Faheem; Singh, Thakur Uttam; Kumar, Tarun; Rungsung, Soya; Rabha, Dipankar Jyoti; Vishwakarma, Anamika; Sukumaran, Susanth V.; Kandasamy, Arunvikram; Parida, Subhashree

doi:10.1016/j.pharep.2017.02.003

Cited by 5 publications

(3 citation statements)

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“…Примечательно, что в группе с применением EPO, несмотря на снижение КЭД, уровень мРНК гена eNos достоверно не увеличился относительно контроля. Это согласуется с данными, полученными Sultan F. и др., демонстрирующими, что EPO, способен угнетать экспрессию eNOS [19]. По всей видимости, это свойство качественно отличает вазотропную активность P-αB от других препаратов эритропоэтинового ряда.…”

Section: Discussionunclassified

11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats.

Korokin

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et al. 2020

Farm. farmakol. (Pâtigorsk)

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The aim of the study was to test whether P-αB can be positioned as a preventing and treating agent for cardiovascular diseases.Materials and methods. The study was performed on sexually mature male Wistar rats. Endothelial dysfunction was modulated by a 7-days intraperitoneal administration of L-NAME at the dose of 2.5 mg/100 g. P-αB, or erythropoietin (EPO), was used for therapy at the dose of 2.5 µg/100 g × 3 times for 7 days, the total dose was 7.5 µg/100 g. The function of endothelium was estimated by an endothelium-dependent and endothelium-independent vasodilation. In addition, a histological assessment of the abdominal aortic wall state and the analysis of eNos, Tnf and Il-1β genes expression were performed. To estimate prothrombotic properties, P-αB and EPO were administered, at the doses of 2.5 and 5 µg/100 g (3 times a day for 7 days, the total doses were 7.5 µg/100 g and 15 µg/100 g, respectively) and on the 8th day, the time of ferric (III) chloride-induced carotid artery thrombosis was estimated.Results. Theresults of the functional tests for endothelium-dependent and endothelium-independent vasodilatation, as well as the histological picture of the aorta have evidenced that P-αB and EPO do not affect L-NAME-induced hypertension but improve the endothelium function. At the same time, P-αB shows a significantly higher endothelial-protective activity, reducing the coefficient of endothelial dysfunction from 5.1±0.15 to 2.72±0.12. In addition, P-αB has significantly increased the expression of eNos and reduced the expression level of Tnf and Il-1β mRNA genes. Carrying out Ferric (III) chloride-induced carotid artery thrombosis has revealed that P-αB (5 µg/100 g × 3 times a day for 7 days, total dose was 15 µg/100 g) has a lower but statistically significant prothrombotic activity than EPO.Conclusion. P-αB can be positioned as an atheroprotector because of its ability to prevent the death of endothelial cells, as well as to reduce remodeling and proinflammatory activation of the vascular wall. However, the prothrombotic properties of P-αB limit its use as a preventing and treating agent for atherosclerosis-associated diseases.

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Section: Discussionunclassified

11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats.

Korokin

Солдатов

Титце

et al. 2020

Farm. farmakol. (Pâtigorsk)

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“…Even it has been shown that rEPO produces a direct pressor effect on bilateral rat renal resistance vessels (Heidenreich et al, 1991) and human placental vessels (Resch et al, 2003). It was previously seen that rEPO impaired nitric oxide production and eNOS mRNA expression in pulmonary vasculature (Sultan et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Recombinant erythropoietin treatment does not alter the blood pressure despite elevated haematological parameters in normotensive Wistar rats

Sultan

Ganaie

Mir

et al. 2020

J Hellenic Vet Med Soc

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Use of erythropoietin (EPO) is believed to be associated with adverse cardiovascular events, especially high blood pressure. Also, its illegal use in blood doping is thought to result in detrimental events both in humans and equines. To test this hypothesis, normal Wistar rats were treated with recombinant erythropoietin (rEPO @ 400 i.u/kg s.c) or normal saline one day apart for one week. Heart rate, systolic, diastolic, mean arterial pressure and blood count were determined. Rats were also observed for their behaviour during the study period. rEPO significantly (P<0.001) increased the erythrocyte count (RBC), haemoglobin (Hb), hematocrit (HCT) and platelet count (PLT) in comparison to control animals. Despite such an increase in hematocrit which in turn increases blood viscosity, the systemic blood pressure and heart rate did not differ between the groups. rEPO treatment did not cause any untoward behavioural change in animals. In conclusion, despite the profound effect on haematological parameters (especially hematocrit), rEPO was without any effect on blood pressure and heart rate and the hypothesis of short-term erythropoietin-induced alterations in cardiac parameters was not verified.

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“…In addition, spasm of the artery may also result in a sharp decrease of the cerebral blood flow, causing ischemia. Vascular tension changes caused by cerebrovascular contracting and relaxing factors play a pivotal role in ischemic cerebrovascular disease [ 1 ], including endothelium-derived relaxing factors such as prostacyclin (PGI 2 ) [ 2 ], nitric oxide (NO) [ 3 ], and endothelium-derived hyperpolarizing factor (EDHF) [ 4 – 7 ]. EDHF plays an important role in physiological and pathological processes.…”

Section: Introductionmentioning

confidence: 99%

Total Flavone of Rhododendron Improves Cerebral Ischemia Injury by Activating Vascular TRPV4 to Induce Endothelium-Derived Hyperpolarizing Factor-Mediated Responses

Han

Chen

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Background Total flavonoids of Rhododendron (TFR) is extracted from Rhododendron, a herbal medicine widely used in China. The main components are flavone compounds such as warfarin, rutin, quercetin, and hyperoside. We investigated the role of TRPV4 channel in the TFR induced endothelium-dependent hyperpolarizing factor- (EDHF-) mediated responses against ischemia/reperfusion injury (IR) in cerebral IR (CIR) rats. Methods The morphological changes of cerebral cortex, the relaxation of cerebral basal artery (CBA), and cell membrane potential recording were studied in CIR rats. The outward potassium current in smooth muscle cell was recorded by whole-cell patch clamp recording. The protein expression of TRPV4, SKca, and IKca was determined. Confocal laser was used to measure the Ca2+ fluorescence intensity. Results After treatment with TFR, the number of pyramidal cells in brain tissue increased and the number of empty or lightly stained cells decreased and these effects were eliminated by using HC-067047, Apamin, or TRAM-34. TFR induced and EDHF-mediated dilatation and hyperpolarization in CBA were also attenuated by using these inhibitors. The increased outward current density elicited by TFR in acutely isolated CBA smooth muscle cells was abolished by using TRAM-34 and Apamin. TFR upregulated the protein expression of TRPV4, SKca, and IKca that was also eliminated by these inhibitors. Laser scanning showed that the increased mean fluorescence intensity of Ca2+ by CIR was decreased by using TFR and that this effect was again eliminated by the above inhibitors. Conclusions We conclude that in the CBA of the CIR rats the protective effect of TFR on ischemic cerebrovascular injury may be related to the activation of the TRPV4 in both endothelium and smooth muscle by increasing its expression and activity. The activation of TRPV4 channel in the endothelium may be linked to the opening of endothelial IKca/SKca channels that induces EDHF-mediated relaxation and hyperpolarization in the smooth muscle cell. In addition, the activation of TRPV4 in the smooth muscle cell in CBA may be linked with the activation of BKCa channel through a TRPV4-dependent pathway, reduce Ca2+ concentration in the cell, and relaxes the vessel. These findings may form a new therapeutic target for protection of ischemic brain injury and facilitate the use of Chinese medicine in brain protection.

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Short-term exposure of erythropoietin impairs endothelial function through inhibition of nitric oxide production and eNOS mRNA expression in the rat pulmonary artery

Cited by 5 publications

References 30 publications

11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats.

11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats.

Recombinant erythropoietin treatment does not alter the blood pressure despite elevated haematological parameters in normotensive Wistar rats

Total Flavone of Rhododendron Improves Cerebral Ischemia Injury by Activating Vascular TRPV4 to Induce Endothelium-Derived Hyperpolarizing Factor-Mediated Responses

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