title: Aging does not affect soluble guanylate cyclase redox state in mouse aortas.
abstract: Aging is associated with endothelial dysfunction, defined as a reduction in nitric oxide (NO) bioavailability. Although the redox state of the NO acceptor soluble guanylate cyclase (sGC) is another determinant factor for its bioavailability and is disturbed by reactive oxygen species (ROS) known to be increased with age, it is unclear whether aging actually has an impact on vascular sGC redox equilibrium. Therefore, this study investigated this issue using two different types of compounds, the sGC stimulator BAY 41-2272 and the sGC activator BAY 60-2770. Plasma thiobarbituric acid-reactive substances (TBARS) levels were markedly higher in aged (19-20 months old) mice than in young (2-3 months old) mice, whereas superoxide levels in endothelium-denuded aortas were not different between the groups. The relaxant response of endothelium-denuded aortas to either BAY 41-2272 or BAY 60-2770 was identical in aged and young mice. In addition, the vascular cGMP production stimulated with BAY 41-2272 or BAY 60-2770 in aged mice was the same level as that in young mice. These findings suggest that aging accompanied by an increase in systemic oxidative stress does not affect vascular smooth muscle ROS generation and sGC redox equilibrium. Unless ROS are increased in vascular smooth muscle, the sGC redox equilibrium might remain unchanged.
authors.affiliation: Department of Pharmacology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimosato
authors.affiliation: Department of Pharmacology, Shiga University of Medical Science, Otsu, Shiga, Japan tawa@belle.shiga-med.ac.jp.
authors.forename: Masashi
authors.initials: M
authors.lastname: Tawa
authors.affiliation: Department of Pharmacology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwasaki
authors.affiliation: Department of Pharmacology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Imamura
authors.affiliation: Department of Pharmacology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Tomio
authors.initials: T
authors.lastname: Okamura
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D001565:Benzoates / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism*; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D008297:Male; D051379:Mice; D009924:Organ Culture Techniques; D010084:Oxidation-Reduction / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000071756:Soluble Guanylyl Cyclase
chemical_list: C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; C528797:4-(((4-carboxybutyl) (2- (5-fluoro-2-((4'-(trifluoromethyl) biphenyl-4-yl)methoxy)phenyl)ethyl) amino)methyl)benzoic acid; D001565:Benzoates; D001713:Biphenyl Compounds; D006845:Hydrocarbons, Fluorinated; D011720:Pyrazoles; D011725:Pyridines; D018160:Receptors, Cytoplasmic and Nuclear; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase
keywords: Aging; nitric oxide; sGC activator; sGC stimulator; soluble guanylate cyclase