Background: Endothelial cells derive nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). The cytochrome P-450-monooxygenase metabolites of arachidonic acid (epoxyeicosatrienoic acids [EETs]) have been suggested to be EDHF. This study was designed to examine the effect of EET(11,12) with regard to the possibility of restoring EDHF function when added into hyperkalemic cardioplegic solution.
Methods: Porcine coronary microartery rings were studied in a myograph. In groups 1 and 2, paired arteries were incubated in either hyperkalemic solution (K+ 20 mmol/L) or Krebs' solution (control). In group 3, the paired arteries were incubated in hyperkalemia plus EET(11,12) (1 x 10(-6.5) mol/L) or hyperkalemia alone (control) at 37 degrees C for 1 hour, followed by Krebs' washout and then precontracted with 1 x 10(-8.5) mol/L U46619. The EDHF-mediated relaxation to EET(11,12) (group 1) or bradykinin (groups 2 and 3) was studied in the presence of N(G)-nitro-L-arginine, indomethacin, and oxyhemoglobin.
Results: After exposure to hyperkalemia, the EDHF-mediated maximal relaxation by bradykinin (72.5% +/- 7.8% versus 41.6% +/- 10.6%; p < 0.05), but not by EET(11,12) (18.4% +/- 3.3% versus 25.1% +/- 4.9%; p > 0.05) was significantly reduced. Incubation with EET(11,12) partially restored EDHF function (33.3% +/- 9.5% versus 62.0% +/- 8.5%; p < 0.05).
Conclusions: In coronary microarteries, hyperkalemia impairs EDHF-mediated relaxation, and EET(11,12) may partially mimic the EDHF function. Addition of EET(11,12) into cardioplegic solution may partially restore EDHF-mediated function reduced by exposure to hyperkalemia.