title: Dimethylarginine dimethylaminohydrolase-1 mediates inhibitory effect of interleukin-10 on angiotensin II-induced hypertensive effects in vascular smooth muscle cells of spontaneously hypertensive rats.
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.
authors.affiliation: Department of Microbiology, College of Medicine, Yeungnam University, 317-1 Daemyungdong, Namgu, Daegu 705-717, Republic of Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine, Yeungnam University, 317-1 Daemyungdong, Namgu, Daegu 705-717, Republic of Korea. Electronic address: heesun@med.yu.ac.kr.
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D016753:Interleukin-10 / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D034622:RNA Interference; D011918:Rats, Inbred SHR; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014662:Vasoconstrictor Agents / Q000494:pharmacology / Q000633:toxicity
chemical_list: D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D016753:Interleukin-10; D001092:Arachidonate 12-Lipoxygenase; D000581:Amidohydrolases; C059999:dimethylargininase
keywords: Angiotensin II; DDAH-1; IL-10