Chronic methionine load-induced hyperhomocysteinemia impairs the relaxation induced by bradykinin in the isolated rat carotid.
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.
Bonaventura
Daniella
D
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.
Tirapelli
Carlos R
CR
de Oliveira
Ana Maria
AM
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
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