title: High oxygen modifies vasodilator effect of cysteine via enhanced oxidative stress and thromboxane production in the rat mesenteric artery.
abstract: Whether high oxygen is harmful to the vascular function is unclear. The present study examined if high oxygen modifies vasodilator effect of cysteine via enhanced oxidative stress and thromboxane production. Rat mesenteric arteries with endothelium at 95 or 50 % oxygen were subjected to isometric force recordings, measurement of thromboxane B2 levels, determination of superoxide and peroxynitrite levels and evaluation of NADPH oxidase subunit protein expression, respectively. L-cysteine (0.01-3 mM) constricted or dilated arteries at 95 and 50 % oxygen, respectively. Thromboxane receptor antagonist SQ-29,548 (1 μM) abolished the constriction at 95 % oxygen. L-cysteine (3 mM) increased levels of thromboxane B2 in arteries upon 95 % oxygen application. L-cysteine relaxed arteries treated with superoxide inhibitor tiron (2 mM) or NADPH oxidase inhibitor gp91ds-tat (1 μM) irrespective of the oxygen concentration while ATP-sensitive K(+) channel inhibitor glibenclamide (1 μM) and cystathionine-γ-lyase (CSE) inhibitor DL-propargylglycine (10 mM) similarly abolished the relaxation. L-cysteine (3 mM) with 95 % oxygen augmented levels of superoxide as well as nitrotyrosine within the artery, concomitantly with enhanced membrane protein expression of NADPH oxidase subunit p47phox. The higher concentration of oxygen attenuates L-cysteine-induced vasodilation via superoxide production mediated by NADPH oxidase along with thromboxane A2 production, resulting in vasoconstriction. The increased levels of superoxide, as well as peroxynitrite, coexist with the impaired vasodilation related to ATP-sensitive K(+) channels and CSE. Higher oxygen with plasma cysteine may cause oxidative stress and vasoconstrictor prostanoid production in blood vessels.
authors.affiliation: Department of Anesthesiology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yasuda
authors.affiliation: Department of Pharmacology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Guo-Gang
authors.initials: GG
authors.lastname: Feng
authors.affiliation: Department of Anesthesiology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Jiazheng
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Nakamura
authors.affiliation: Department of Physiology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Hisaki
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Physiology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Motohiko
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Anesthesiology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Anesthesiology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi, 480-1195, Japan. hkinoshi@aichi-med-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kinoshita
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D003545:Cysteine / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000494:pharmacology*; D030421:Peroxynitrous Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D013931:Thromboxanes / Q000378:metabolism*; D014664:Vasodilation
chemical_list: D000480:Alkynes; D006023:Glycoproteins; D013931:Thromboxanes; C473031:gp91ds-tat protein, chimeric; D013481:Superoxides; D030421:Peroxynitrous Acid; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; C009055:propargylglycine; D019255:NADPH Oxidases; D003545:Cysteine; D010100:Oxygen; D005905:Glyburide; D005998:Glycine
keywords: Cystathionine-γ-lyase; Cysteine; NADPH oxidase; Superoxide