Epoxyeicosatrienoic acids (EET(11,12)) may partially restore endothelium-derived hyperpolarizing factor-mediated function in coronary microarteries.
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.
Zou
W
W
Department of Surgery, The Chinese University of Hong Kong, Hong Kong SAR.
Yang
Q
Q
Yim
A P
AP
He
G W
GW
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology*
D001685:Biological Factors; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; D015126:8,11,14-Eicosatrienoic Acid; D011188:Potassium