title: Thyroid hormone exacerbates vasoconstriction in insulin resistance: the role of ONOO(-).
abstract: Insulin resistance has been proposed to play a pivotal role in vasoconstriction due to increased oxidative stress. Hyperthyroidism would amplify cardiovascular disease risk in diabetic patients, though thyroid hormone advance vascular relaxation and reduce vascular contraction by virtue of NO production in vascular smooth muscle cells (VSMCs). Thus, we aimed to investigate the vascular tone and its underlying mechanism in insulin resistance accompanied by hyperthyroidism. Vascular reactivity studies showed that endothelium-denuded thoracic aortic rings from rats fed with high-fat high-sucrose (HFHS) diet and L-T4 (HFHS+L-T4) exhibited a stronger contractile response to noradrenaline than HFHS rats, which was reversed by L-NAME and GSH. Furthermore, rat thoracic aortic smooth muscle cells (A10) simultaneously stimulated with high glucose insulin (high Glc/Ins) and T3 demonstrated lower NO, superoxide anion ( [Formula: see text] ) levels, and higher iNOS, nitrite ( [Formula: see text] ), peroxynitrite (ONOO(-)) levels than that treated with T3 only. Excessive ONOO(-) markedly aggravated oxidative stress. Thus, we hypothesized that the elevated concentration of ONOO(-) which is generated by NO and [Formula: see text] could be critically instrumental in the progression of vasoconstriction by increasing oxidative stress.
authors.affiliation: Experimental and Teaching Center of Medical Basis for Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: D H
authors.initials: DH
authors.lastname: Hu
authors.affiliation: Experimental and Teaching Center of Medical Basis for Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: J
authors.initials: J
authors.lastname: Peng
authors.affiliation: Experimental and Teaching Center of Medical Basis for Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Experimental and Teaching Center of Medical Basis for Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: H L
authors.initials: HL
authors.lastname: Zheng
authors.affiliation: Experimental and Teaching Center of Medical Basis for Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: S M
authors.initials: SM
authors.lastname: Yan
authors.affiliation: Experimental and Teaching Center of Medical Basis for Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Y T
authors.initials: YT
authors.lastname: Zhang
authors.affiliation: Experimental and Teaching Center of Medical Basis for Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Q H
authors.initials: QH
authors.lastname: Guan
authors.affiliation: Experimental and Teaching Center of Medical Basis for Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China. Electronic address: g637cpu@163.com.
authors.forename: Q L
authors.initials: QL
authors.lastname: Ding
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D006980:Hyperthyroidism / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D013963:Thyroid Hormones; D014284:Triiodothyronine; D030421:Peroxynitrous Acid; D009569:Nitric Oxide
keywords: 3, 3׳, 5-Triiodo-l-thyronine sodium salt (PubChem CID: 23666110); Glutathione (PubChem CID: 124886); Hyperthyroidism; Insulin resistance; LY294002 (PubChem CID: 3973); Levothyrocine sodium (PubChem CID: 23666112); N-nitro-l-arginine methyl ester (PubChem CID: 39836); Noradrenaline bitartrate (PubChem CID: 297812); Peroxynitrite ion; Pioglitazone hydrochloride (PubChem CID: 60560); Sodium nitroprusside (PubChem CID: 11963579); Vasoconstriction