Reversal of bradykinin-induced relaxation to contraction after interferon-gamma in bovine isolated mesenteric arteries

Eur J Pharmacol. 1994 Aug 11;261(1-2):111-20. doi: 10.1016/0014-2999(94)90308-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Amino Acid Sequence
  • Animals
  • Bradykinin / antagonists & inhibitors*
  • Bradykinin / pharmacology
  • Cattle
  • Cycloheximide / pharmacology
  • In Vitro Techniques
  • Interferon-gamma / pharmacology*
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / metabolism
  • Methylene Blue / pharmacology
  • Molecular Sequence Data
  • Muscle Contraction / drug effects*
  • Muscle Relaxation / drug effects*
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Nitric Oxide / metabolism
  • Prostaglandin Endoperoxides, Synthetic / pharmacology
  • Receptors, Bradykinin / drug effects
  • Thromboxane A2 / analogs & derivatives
  • Thromboxane A2 / pharmacology
  • Up-Regulation / drug effects
  • Vasoconstrictor Agents / pharmacology


  • Prostaglandin Endoperoxides, Synthetic
  • Receptors, Bradykinin
  • Vasoconstrictor Agents
  • Nitric Oxide
  • Thromboxane A2
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Interferon-gamma
  • Cycloheximide
  • Bradykinin
  • Methylene Blue