In vivo stimulatory effect of erythropoietin on endothelial nitric oxide synthase in cerebral arteries

Santhanam, Anantha Vijay R.; Smith, Leslie; Nath, Karl A.; Katušić, Zvonimir S.

doi:10.1152/ajpheart.00045.2006

Cited by 41 publications

(36 citation statements)

References 45 publications

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“…In contrast, in chronic lung disease, endothelium-dependent vasodilatation in response to acetylcholine is inhibited in patients with polycythemia with high hematocrit who may have very low EPO levels, and this inhibition can be reversed by normalization of blood hemoglobin concentration, suggesting that in the absence of high elevation of EPO levels, increased hemoglobin decreases NO bioavailability [76]. Adenoviral vector encoding EPO injected into brain in rabbits stimulated endothelial nitric oxide synthase expression and NO production, increased cGMP in transduced arteries, augmented endothelium-dependent relaxation to acetylcholine and attenuated contractile response to histamine by 48 h after injection without affecting red blood cell count [77]. The participation of EPO in regulation of NO production and blood flow may contribute to its neuroprotective role in brain ischemia.…”

Section: Epo and Nitric Oxide Productionmentioning

confidence: 99%

Role of erythropoietin in the brain

Noguchi

Asavaritikrai

Teng

et al. 2007

Critical Reviews in Oncology/Hematology

206

159

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Multi-tissue erythropoietin receptor (EPO-R) expression provides for erythropoietin (EPO) activity beyond its known regulation of red blood cell production. This review highlights the role of EPO and EPO-R in brain development and neuroprotection. EPO-R brain expression includes neural progenitor cells (NPC), neurons, glial cells and endothelial cells. EPO is produced in brain in a hypoxia sensitive manner, stimulates NPC proliferation and differentiation, and neuron survival, and contributes to ischemic preconditioning. Mice lacking EPO or EPO-R exhibit increased neural cell apoptosis during development before embryonic death due to severe anemia. EPO administration provides neural protection in animal models of brain ischemia and trauma, reducing the extent of injury and damage. EPO stimulation of endothelial cells contributes to neuroprotection and is of particular importance since only low levels of EPO appear to cross the blood-brain barrier when administered at high dose intravenously. The therapeutic potential of EPO for brain ischemia/trauma and neurodegenerative diseases has shown promise in early clinical trial and awaits further validation.

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Section: Epo and Nitric Oxide Productionmentioning

confidence: 99%

Role of erythropoietin in the brain

Noguchi

Asavaritikrai

Teng

et al. 2007

Critical Reviews in Oncology/Hematology

206

159

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“…At the same time, EPO has shown potent ability to suppress the inducible NO synthase (iNOS)-mediated NO production and peroxynitrite formation, thereby attenuating cytotoxicity and vascular dysfunction during experimental shock induced by zymosan or LPS [36,38,43]. Besides inhibition of iNOS, EPO is well known to induce expression of endothelial NO synthase (eNOS) [75]. Thus, recovery of the regulation of the microcirculation by eNOS-mediated nitric oxide may also contribute to the protection achieved by EPO treatment [76].…”

Section: Antioxidant Properties Of Epo During Ali/ardsmentioning

confidence: 99%

Erythropoetin as a novel agent with pleiotropic effects against acute lung injury

Kakavas

Demestiha

Vasileiou

et al. 2010

Eur J Clin Pharmacol

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Current pharmacotherapy for acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) is not optimal, while the biological and physiological complexity of these severe lung injury syndromes requires consideration of combined-agent treatments or agents with pleiotropic action. In this regard, exogenous erythropoietin (EPO) represents a possible candidate since a number of preclinical studies have revealed beneficial effects of EPO administration in various experimental models of ALI. Taken together, this treatment strategy is not a single mediator approach, but it rather provides protection by modulating multiple levels of early signaling pathways involved in apoptosis, inflammation and peroxidation, potentially restoring overall homeostasis. Furthermore, EPO appears to confer vascular protection by promoting angiogenesis. However, only preliminary studies exist and more experimental and clinical studies are necessary for the clarification of the efficacy and potentially cytoprotective mechanisms of EPO action. In addition to the attempts to optimize the dose and timing of EPO administration, it would be of great value to minimize any potential toxicity, which is essential for EPO to fulfil its role as a potential candidate for the treatment of ALI in routine clinical practice. The present article reviews recent advances that have elucidated biological and biochemical activities of EPO which may be potentially applicable for ALI/ARDS management.

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“…19,20 Twenty-four hours after injection, rabbits were euthanized and the basilar arteries were isolated.…”

Section: In Vivo Administration Of Epcsmentioning

confidence: 99%

“…20,21 Blots were incubated with monoclonal antibodies (1:500 dilution) against COX-1 (Cayman), COX-2 (BD Transduction), inducible NO synthase (iNOS) (BD Transduction), actin (1:2000; Santa Cruz Biotech), polyclonal antibodies against endothelial NO synthase (eNOS) (BD Transduction), and PGI 2 synthase (Cayman).…”

Section: Western Blotmentioning

confidence: 99%

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Endothelial Progenitor Cells Stimulate Cerebrovascular Production of Prostacyclin By Paracrine Activation of Cyclooxygenase-2

Santhanam

Smith

et al. 2007

Circulation Research

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Abstract-In the present study we hypothesized that endothelial progenitor cells (EPCs) enhance production of vasoprotective substances in cerebral arteries. Isolated mononuclear cells from rabbit peripheral blood were cultured in endothelial growth medium (EGM-2) for 7 days to yield EPCs. Rabbit basilar arteries were exposed to autologous EPCs (Ϸ5ϫ10 5 cells) in vitro or in vivo. Twenty-four hours after intracisternal delivery of autologous EPCs, basilar arteries were isolated and expression of vasoregulatory proteins, production of prostacyclin (PGI 2 ), and cAMP were determined. Arteries transplanted with EPCs demonstrated increased protein expression of cyclooxygenase-2 and PGI 2 in adventitia, media, and endothelium. Furthermore, production of PGI 2 and arterial content of cAMP, second messenger for PGI 2 , were significantly augmented after transplantation of EPCs. In contrast, production of thromboxane A 2 was significantly reduced, whereas production of prostaglandin E 2 remained unchanged. The increased production of PGI 2 and arterial content of cAMP were inhibited only by a selective cyclooxygenase-2 inhibitor, NS-398. In vitro or in vivo treatment of basilar artery with conditioned media from EPCs also caused increase in cyclooxygenase-2 and PGI 2 synthase protein expression associated with elevation of cAMP. Our results suggest that in cerebral arteries, paracrine effect of EPCs promotes vasoprotection by increasing PGI 2 production and intracellular concentration of cAMP. This effect appears to be mediated by activation of arachidonic acid metabolism via stimulation of cyclooxygenase-2/PGI 2 synthase pathway.

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In vivo stimulatory effect of erythropoietin on endothelial nitric oxide synthase in cerebral arteries

Abstract: . In vivo stimulatory effect of erythropoietin on endothelial nitric oxide synthase in cerebral arteries.

Cited by 41 publications

References 45 publications

Role of erythropoietin in the brain

Role of erythropoietin in the brain

Erythropoetin as a novel agent with pleiotropic effects against acute lung injury

Endothelial Progenitor Cells Stimulate Cerebrovascular Production of Prostacyclin By Paracrine Activation of Cyclooxygenase-2

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