title: Incubation of rat aortic rings produces a specific reduction in agonist-evoked contraction: effect of age of donor.
abstract: We studied the effect of age on the response of aortic rings to injury produced by three days' incubation, and the mechanism of this response. Five-mm rings of the thoracic aorta isolated from Wistar rats were incubated or not in culture medium. Isometric contraction evoked by agonists (norepinephrine or serotonin) or high [K(+)](e) was determined in the presence and absence of endothelium. Experiments were repeated in the presence of propranolol (0.3 microM), polymixin B (36 microM), pyrrolidine dithiocarbamate (50 microM) or glutathione (3 mM). Inductible NO-synthase and cyclo-oxygenase-2 mRNA were determined by real-time PCR, and glutathione-related enzymes and catalase activity by spectrophotometry. Incubation reduced the isometric contraction evoked by agonists but not by high [K(+)](e). The reduction in agonist-evoked contraction was greater in rings from adult (norepinephrine Emax-80%) than in young (-40%) rats. The removal of the endothelium had no effect. The reduction in norepinephrine-evoked contraction was not due to endotoxin contamination, beta-adrenoceptor-mediated dilation or any change in ring structure (no fibrosis or edema). Inductible NO-synthase (but not cyclo-oxygenase-2) mRNA increased on incubation. N(G)-nitro-L-arginine methyl ester partially restored contractility in rings from adult animals, further addition of an anti-oxidant restored norepinephrine-evoked contraction. Catalase fell with age and glutathione reductase increased upon incubation in rings from young donors only. In conclusion, incubation of the aorta produces a specific reduction in agonist-evoked contraction that involves induction of smooth muscle cell oxidative stress and iNOS. The reaction is greater in rings from older animals.
authors.affiliation: Cardiovascular Research Group (EA 3448), Faculté de Pharmacie, UHP-Nancy 1, 5 rue Albert Lebrun, 54001 Nancy Cedex, France.
authors.forename: Angela C
authors.initials: AC
authors.lastname: Resende
authors.forename: Aurore
authors.initials: A
authors.lastname: Tabellion
authors.forename: Sophie
authors.initials: S
authors.lastname: Nadaud
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lartaud
authors.forename: Denyse
authors.initials: D
authors.lastname: Bagrel
authors.forename: Sebastien
authors.initials: S
authors.lastname: Faure
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Atkinson
authors.forename: Christine
authors.initials: C
authors.lastname: Capdeville-Atkinson
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology*; D002374:Catalase / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D017931:DNA Primers; D005978:Glutathione / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000494:pharmacology; D013053:Spectrophotometry; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors
chemical_list: D003470:Culture Media; D017931:DNA Primers; D007527:Isoenzymes; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D012701:Serotonin; D011433:Propranolol; D002374:Catalase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D005978:Glutathione; D011188:Potassium; D009638:Norepinephrine