Fig. 4. The IDO pathway metabolite Kyn regulates vascular tone.
(a) Relaxation of porcine coronary arteries in response to addition of Trp. Fresh porcine circumflex arteries with intact or denuded endothelium (EC) were incubated for 20 h at 37 °C in M199 in the absence or presence of 400 ng IFNγ/mL. Arteries were then removed, washed and incubated with 300 μM N-nitro-l-arginine methyl ester and 10 μM indomethacin for 30 min and pre-contracted with U-46619 to 50-60% of maximum force. Relaxation was determined in response to addition of Trp (8 mM final concentration). *P<0.05 versus EC-denuded and 1-Me-Trp-treated groups. (b) Contraction of porcine coronary artery in response to U-46619 in control preparations (❍) and in preparations pre-treated with 6 mM Kyn for 1 h (●). *P<0.05 versus control. (c) Relaxation of denuded vessel rings (▲) or rings with intact EC in response to added DMSO (❍, vehicle control) or Kyn (●). *P<0.05 versus control. (d, e) Trp, Kyn or sodium nitroprusside (SNP) was injected into spontaneously hypertensive rats via the femoral vein to give final blood concentrations ranging from 0.15 – 1.5 mM (for Kyn and Trp) and 0.15 – 1.5 μM (SNP), with systolic blood pressure being monitored continuously. We assumed a total blood volume of 17 mL for the 250 g rats used. (d) Typical blood pressure responses elicited by 1.5 mM of either Kyn or Trp, or 1.5 μM SNP. (e) Dose-dependent changes in systolic blood pressure following injection of Kyn (●), Trp (Δ) or SNP (❍). The results show mean±SEM of four (a), six (b, c) or three (e) independent experiments.