title: Urotensin-II activates L-arginine/nitric oxide pathway in isolated rat aortic adventitia.
abstract: Urotensin-II (U-II), a cyclic peptide widely expressed in blood vessels, has diverse vascular actions that range from potent vasoconstriction to vasodilation. Although, U-II-induced vasodilation has been shown to be partially dependent on nitric oxide (NO), the involvement of vascular adventitia-derived NO, remains unknown. The present study aimed to elucidate the activation of U-II on L-arginine/NO pathway in isolated rat aortic adventitia. In adventitia of thoracic and abdominal aortas, the l-arginine/NO pathway was similarly characterized: the uptake of l-[(3)H]arginine was Na(+)-independent, with the peak occurring over around 40 min incubation; the total NO synthase (NOS) activity was mostly calcium-independent (>90%), and significantly inhibited by a specific iNOS inhibitor AMT; the production of NO metabolites nitrate and nitrite (NO(x)) was stimulated by L-arginine but not by D-arginine. In aortic adventitia exposed to rat U-II (10(-9) and 10(-8)M) for 6 h, the V(max) of l-[(3)H]arginine uptake over 40 min incubation was significantly increased, while the K(m) of l-[(3)H]arginine uptake showed no significant change. Besides, the iNOS mRNA level was up-regulated, the total NOS activity, largely calcium-independent, was significantly induced, and the NO(x) production was significantly stimulated by U-II. According to the same protocol as U-II, the positive control lipopolysaccharide (LPS, 10 microg/ml), which had been established to activate adventitial L-arginine/NO pathway, increased l-[(3)H]arginine uptake, iNOS activity and NO(x) production to a greater extent than U-II. In addition, the total NOS activities induced by 3 and 6h incubation of U-II and LPS were significantly inhibited by a specific inhibitor of protein synthesis, actinomycin D. In conclusion, the results showed that rat U-II activated L-arginine/NOS/NO pathway in rat aortic adventitia, suggesting a potential contributive role of adventitia-derived NO in the vasodilator response of U-II.
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai 200433, PR China. linlil@msu.edu
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Ding
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Zhang
authors.forename: Yong-Fen
authors.initials: YF
authors.lastname: Qi
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Yuan
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects*; D001013:Aorta, Thoracic / Q000187:drug effects*; D001120:Arginine / Q000378:metabolism*; D003238:Connective Tissue / Q000187:drug effects*; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects; D014579:Urotensins / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014579:Urotensins; D003609:Dactinomycin; D009569:Nitric Oxide; C029677:urotensin II; D001120:Arginine