Dimethylarginine dimethylaminohydrolase-1 mediates inhibitory effect of interleukin-10 on angiotensin II-induced hypertensive effects in vascular smooth muscle cells of spontaneously hypertensive rats |
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| Affiliation: | 1. Division of Fundamental Neurobiology, Toronto Western Research Institute, UHN, Toronto, ON, Canada;2. Department of Biomedical and Molecular Sciences, Queen''s University, Kingston, ON, Canada;3. Division of Clinical Pharmacology & Toxicology, The Hospital for Sick Children, Toronto, ON, Canada;4. Department of Medicine (Neurology), University of Toronto, Toronto, ON, Canada;5. Department of Physiology, University of Toronto, Toronto, ON, Canada;6. Department of Biology, York University, Toronto, ON, Canada;7. Department of Psychology, York University, Toronto, ON, Canada;8. Robarts Research Institute and Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada;1. Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China;2. Department of Neurosurgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China;3. Key Laboratory of Myocardial Ischemia Mechanism and Treatment Ministry, Harbin 150086, China;1. Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Curie 9, 85-090 Bydgoszcz, Poland;2. Second Department of Cardiology, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, K. Ujejskiego 75, 85-168 Bydgoszcz, Poland;3. Department of Pathophysiology of Hearing and Balance System, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Curie 9, 85-090 Bydgoszcz, Poland |
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| Abstract: | In hypertension studies, anti-inflammatory cytokine interleukin-10 (IL-10) has been shown to prevent angiotensin II (Ang II)-induced vasoconstriction and regulate vascular function by down-regulating pro-inflammatory cytokine and superoxide production in vascular cells. However, little is known about the mechanism behind the down-regulatory effect of IL-10 on Ang II-induced hypertensive mediators. In this study, we demonstrated the effects of IL-10 on expression of dimethylarginine dimethylaminohydrolase (DDAH)-1, a regulator of NO bioavailability, as well as the down-regulatory mechanism of action of IL-10 in relation to Ang II-induced hypertensive mediator expression and cell proliferation in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR). IL-10 increased DDAH-1 but not DDAH-2 expression and increased DDAH activity. Additionally, IL-10 attenuated Ang II-induced DDAH-1 inhibition in SHR VSMCs. Increased DDAH activity due to IL-10 was mediated mainly through Ang II subtype II receptor (AT2 R) and AMP-activated protein kinase (AMPK) activation. DDAH-1 induced by IL-10 partially mediated the inhibitory action of IL-10 on Ang II-induced 12-lipoxygenase (LO) and endothelin (ET)-1 expression in SHR VSMCs. In addition, the inhibitory effect of IL-10 on proliferation of Ang II-induced VSMCs was mediated partially via DDAH-1 activity. These results suggest that DDAH-1 plays a potentially important role in the anti-hypertensive activity of IL-10 during Ang II-induced hypertension. |
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| Keywords: | IL-10 DDAH-1 Angiotensin II |
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