title: Chronic methionine load-induced hyperhomocysteinemia impairs the relaxation induced by bradykinin in the isolated rat carotid.
abstract: This study investigates the effects of chronic methionine intake on bradykinin (BK)-relaxation. Vascular reactivity experiments were performed on carotid rings from male Wistar rats. Treatment with methionine (0.1, 1 or 2 g kg(-1) per day) for 8 and 16 weeks, but not for 2 and 4 weeks, reduced the relaxation induced by BK. Indomethacin, a non-selective cyclooxygenase (COX) inhibitor, and SQ29548, a selective thromboxane A(2) (TXA(2))/prostaglandin H(2) (PGH(2)) receptor antagonist prevented the reduction in BK-relaxation observed in the carotid from methionine-treated rats. Conversely, AH6809, a selective prostaglandin F(2alpha) (PGF(2alpha)) receptor antagonist did not alter BK-relaxation in the carotid from methionine-treated rats. The nitric oxide synthase (NOS) inhibitors L-NAME, L-NNA and 7-nitroindazole reduced the relaxation induced by BK in carotids from control and methionine-treated rats. In summary, we found that chronic methionine intake impairs the endothelium-dependent relaxation induced by BK and this effect is due to an increased production of endothelial vasoconstrictor prostanoids (possibly TXA(2)) that counteracts the relaxant action displayed by the peptide.
authors.affiliation: Laboratory of Pharmacology, Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences, University of São Paulo (USP), Avenida do Café s/n, Ribeirão Preto, SP, CEP 14040-903, Brazil.
authors.forename: Daniella
authors.initials: D
authors.lastname: Bonaventura
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Tirapelli
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology / Q000502:physiology*; D002317:Cardiovascular Agents / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology*; D002908:Chronic Disease; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020138:Hyperhomocysteinemia / Q000503:physiopathology*; D007191:Indazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008715:Methionine / Q000008:administration & dosage*; D009126:Muscle Relaxation / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology; D044004:Xanthones / Q000494:pharmacology
chemical_list: D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D007191:Indazoles; D011448:Prostaglandin Antagonists; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D014665:Vasodilator Agents; D044004:Xanthones; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D008715:Methionine; D019001:Nitric Oxide Synthase; D001920:Bradykinin; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin