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.