REVERSAL OF BRADYKININ-INDUCED RELAXATION TO CONTRACTION AFTER INTERFERON-GAMMA IN BOVINE ISOLATED MESENTERIC-ARTERIES

Bovine isolated mesenteric arterial rings were preincubated for 20 h w ith interferon-gamma (100 U ml(-1)) and relaxation in response to brad ykinin (10(-12) to 3 x 10(-8) M) was then measured isometrically in an organ bath. Interferon-gamma pretreatment for 20 h markedly attenuate d the endothelium-dependent bradykinin relaxation in arteries precontr acted with 9,11-dideoxy-11 alpha,9 alpha-epoxymethano prostaglandin F- 2 alpha (U46619), and the relaxation was reversed to contraction at th e highest bradykinin concentrations (-72 +/- 5% for control vs. + 6 +/ 10% for interferon-gamma). Cycloheximide (20 mu g ml(-1)) present dur ing the 20-h preincubation completely prevented the interferon-gamma e ffect. Methyl-L-arginine (1 mM) treatment during the 20-h preincubatio n also inhibited the interferon-gamma effect on bradykinin relaxation (- 47 +/- 18% for interferon-gamma and methyl-L-arginine), which sugge sts involvement of nitric oxide during the 20-h preincubation with int erferon-gamma. In control arteries, des-Arg(9)-bradykinin, a bradykini n B-1 receptor agonist, evoked contractions, which were augmented in r ings preincubated for 20 h with interferon-gamma. The bradykinin B-1 r eceptor antagonist, des-Arg(9)-Leu(8)-bradykinin (2 mu M), present in the organ bath in combination with methyl-L-arginine (1 mM) only prese nt during the 20-h preincubation with interferon-gamma completely rest ored the bradykinin relaxation (- 79 +/- 12%). We suggest two mechanis ms. Firstly, prolonged nitric oxide release induced by interferon-gamm a during the 20-h preincubation may inhibit bradykinin stimulated endo thelium-derived nitric oxide release and action. Secondly, interferon- gamma caused upregulation of the bradykinin B-1 receptor-mediated cont raction, which may contribute to the decrease in bradykinin-induced va sodilation and cause a reversal to contraction.