title: The enhancement of TXA2receptors-mediated contractile response in intrarenal artery dysfunction in type 2 diabetic mice.
abstract: Thromboxane A2(TXA2) has been implicated in the pathogenesis of diabetic vascular complications, although the underlying mechanism remains unclear. The present study investigated the alterations in TXA2receptor signal transduction in type 2 diabetic renal arteries. The contraction of renal arterial rings in control (db/m+) mice and type 2 diabetic (db/db) mice was measured by a Multi Myograph System. Intracellular calcium concentration ([Ca2+]i) in vascular smooth muscle cells was measured by Fluo-4/AM dye and confocal laser scanning microscopy. Quantitative real-time PCR and Western blot analysis were used to determine gene and protein expression levels, respectively. A stable TXA2mimic U46619 caused markedly stronger dose-dependent contractions in the renal arteries of db/db mice than in those of db/m+mice. This response was completely blocked by a TXA2receptor antagonist GR32191 and significantly inhibited by U73122. U46619-induced vasoconstriction was increased in the presence of nifedipine in db/db mice compared with that in db/m+mice, whereas the response to U46619 did not differ between the two groups in the presence of SKF96365. Sarcoplasmic reticulum Ca2+release-mediated and CaCl2-induced contractions did not differ between the two groups. In db/db mice, store-operated Ca2+(SOC) entry-mediated contraction in the renal arteries and SOC entry-mediated Ca2+influx in smooth muscle cells were significantly increased. And the gene and protein expressions of TXA2receptors, Orai1 and Stim1 were upregulated in the diabetic renal arteries. Therefore the enhancement of U46619-induced contraction was mediated by the upregulation of TXA2receptors and downstream signaling in the diabetic renal arteries.
authors.affiliation: Guangdong Cardiovascular Institute, PR China; Department of Medical Research, Guangdong General Hospital, PR China; Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Su-Juan
authors.initials: SJ
authors.lastname: Kuang
authors.affiliation: Department of Radiology, Intervention Radiology Institute, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Jie-Sheng
authors.initials: JS
authors.lastname: Qian
authors.affiliation: Guangdong Cardiovascular Institute, PR China; Department of Medical Research, Guangdong General Hospital, PR China; Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Guangdong Cardiovascular Institute, PR China; Department of Medical Research, Guangdong General Hospital, PR China; Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Rao
authors.affiliation: Guangdong Cardiovascular Institute, PR China; Department of Medical Research, Guangdong General Hospital, PR China; Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Chen
authors.affiliation: Guangdong Cardiovascular Institute, PR China; Department of Medical Research, Guangdong General Hospital, PR China; Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Meng-Zhen
authors.initials: MZ
authors.lastname: Zhang
authors.affiliation: Guangdong Cardiovascular Institute, PR China; Department of Medical Research, Guangdong General Hospital, PR China; Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Shan
authors.affiliation: Guangdong Cardiovascular Institute, PR China; Department of Medical Research, Guangdong General Hospital, PR China; Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Qiu-Xiong
authors.initials: QX
authors.lastname: Lin
authors.affiliation: Guangdong Cardiovascular Institute, PR China; Department of Medical Research, Guangdong General Hospital, PR China; Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Xue
authors.affiliation: Guangdong Cardiovascular Institute, PR China; Department of Medical Research, Guangdong General Hospital, PR China; Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Shu-Lin
authors.initials: SL
authors.lastname: Wu
authors.affiliation: Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Guangdong Cardiovascular Institute, PR China; Department of Medical Research, Guangdong General Hospital, PR China; Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China. Electronic address: gghicu@163.com.
authors.forename: Chun-Bo
authors.initials: CB
authors.lastname: Chen
authors.affiliation: Guangdong Cardiovascular Institute, PR China; Department of Medical Research, Guangdong General Hospital, PR China; Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China. Electronic address: chunyudeng@126.com.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Deng
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology*; D015220:Calcium Channels / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D015220:Calcium Channels; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
keywords: Ca(2+) channel; Diabetic mice; Renal artery; SOC entry; U46619; Vasoconstriction