Epoxyeicosatrienoic acids (EET11,12) may partially restore endothelium-derived hyperpolarizing factor-mediated function in coronary microarteries

Background. Endothelial cells derive nitric oxide, prostacyclin, and endoth elium-derived hyperpolarizing factor (EDHF). The cytochrome P-450-monooxyge nase metabolites of arachidonic acid (epoxyeicosatrienoic acids MEW) have b een suggested to be EDHF. This study was designed to examine the effect of EET11,12 with regard to the possibility of restoring EDHF function when add ed 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 solut ion (K+ 20 mmol/L) or Krebs' solution (control). In group 3, the paired art eries were incubated in hyperkalemia plus EET11,12 (1 x 10(-6.5) mol/L) or hyperkalemia alone (control) at 37 degreesC for 1 hour, followed by Krebs' washout and then precontracted with 1 x 10(-8.5) mol/L U46619. The EDHF-med iated relaxation to EET11,12 (group 1) or bradykinin (groups 2 and 3) was s tudied in the presence of N-G-nitro-L-arginine, indomethacin, and oxyhemogl obin. Results. After exposure to hyperkalemia, the EDHF-mediated maximal relaxati on by bradykinin (72.5% +/- 7.8% versus 41.6% +/- 10.6%; p < 0.05), but not by EET11,12 (18.4% +/- 3.3% versus 25.1% +/- 4.9%; p > 0.05) was significa ntly reduced. Incubation with EET11,12 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 EET11,12 may partially mimic the EDHF function. Addition of EET,1,12 into cardioplegic solution may partially restore EDHF-mediated fu nction reduced by exposure to hyperkalemia. (C) 2001 by The Society of Thor acic Surgeons.