Different Role of Epoxyeicosatrienoic Acids (EET 11,12 ) in Endothelium‐Derived Hyperpolarizing Factor‐Mediated Relaxation in Porcine Coronary and Pulmonary Micro‐Arteries

Abstract

Objectives: Endothelium-derived hyperpolarizing factor (EDHF) plays a key role in vasorelaxation and the cytochrome P450-monooxygenase metabolites of arachidonic acid epoxyeicosatrienoic acids (EETs), such as EET11,12, have been suggested to be EDHF in various vasculatures. However, little is known about the role of EET11,12 in the coronary and pulmonary circulation, especially in microcirculation. The present study was designed to examine the role of EET11,12 in porcine coronary and pulmonary micro-arteries. Methods: Porcine coronary and pulmonary micro-arteries (diameter 200-450 μm) were studied in a myograph (n = 8 in each group). The artery rings were set at the 90% of the circumference at 100 mm Hg for coronary or 30 mm Hg for pulmonary micro-arteries, respectively. After precontraction with U46619 (−8.2 log M for coronary and −7.5 log M for pulmonary micro-arteries), EET11,12 (−10 ∼−6.5 log M) or bradykinin (BK, −10 ∼−6.5 log M)-induced relaxation was established in the presence of inhibitors for cyclooxygenase (indomethacin, 7 μM), nitric oxide (NO) synthetase (NG-nitro-L-arginine, 300 μM), and NO scavenger oxyhemoglobin (20 μM). Results: EET11,12 induced a dose-dependent relaxation in coronary micro-arteries with the maximal relaxation of 18.3 ± 3.3% that was significantly less than the relaxation induced by BK (72.5 ± 7.8%; P < 0.001). In contrast, in pulmonary micro-arteries, BK induced a marked relaxation (69.6 ± 6.3%) whereas EET11,12 did not have any effect. Conclusion: In porcine coronary micro-arteries, EET11,12 may partially mimic the action of EDHF whereas in pulmonary arteries, this substance is unlikely involved in the EDHF-mediated relaxation.