title: Reversal of bradykinin-induced relaxation to contraction after interferon-gamma in bovine isolated mesenteric arteries.
abstract: Bovine isolated mesenteric arterial rings were preincubated for 20 h with interferon-gamma (100 U ml-1) and relaxation in response to bradykinin (10(-12) to 3 x 10(-8) M) was then measured isometrically in an organ bath. Interferon-gamma pretreatment for 20 h markedly attenuated the endothelium-dependent bradykinin relaxation in arteries precontracted with 9,11-dideoxy-11 alpha,9 alpha-epoxymethano prostaglandin F2 alpha (U46619), and the relaxation was reversed to contraction at the highest bradykinin concentrations (-72 +/- 5% for control vs. + 6 +/- 10% for interferon-gamma). Cycloheximide (20 micrograms ml-1) present during the 20-h preincubation completely prevented the interferon-gamma effect. Methyl-L-arginine (1 mM) treatment during the 20-h preincubation also inhibited the interferon-gamma effect on bradykinin relaxation (-47 +/- 18% for interferon-gamma and methyl-L-arginine), which suggests involvement of nitric oxide during the 20-h preincubation with interferon-gamma. In control arteries, des-Arg9-bradykinin, a bradykinin B1 receptor agonist, evoked contractions, which were augmented in rings preincubated for 20 h with interferon-gamma. The bradykinin B1 receptor antagonist, des-Arg9-Leu8-bradykinin (2 microM), present in the organ bath in combination with methyl-L-arginine (1 mM) only present during the 20-h preincubation with interferon-gamma completely restored the bradykinin relaxation (-79 +/- 12%). We suggest two mechanisms. Firstly, prolonged nitric oxide release induced by interferon-gamma during the 20-h preincubation may inhibit bradykinin stimulated endothelium-derived nitric oxide release and action. Secondly, interferon-gamma caused upregulation of the bradykinin B1 receptor-mediated contraction, which may contribute to the decrease in bradykinin-induced vasodilation and cause a reversal to contraction.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Utrecht University, Netherlands.
authors.forename: S J
authors.initials: SJ
authors.lastname: De Kimpe
authors.forename: W
authors.initials: W
authors.lastname: Tielemans
authors.forename: D
authors.initials: D
authors.lastname: Van Heuven-Nolsen
authors.forename: F P
authors.initials: FP
authors.lastname: Nijkamp
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002417:Cattle; D003513:Cycloheximide / Q000494:pharmacology; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D008751:Methylene Blue / Q000494:pharmacology; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D018002:Receptors, Bradykinin / Q000187:drug effects; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D011450:Prostaglandin Endoperoxides, Synthetic; D018002:Receptors, Bradykinin; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D007371:Interferon-gamma; D003513:Cycloheximide; D001920:Bradykinin; D008751:Methylene Blue