The ‘EDHF’ Antagonist 14, 15 Epoxyeicosa-5(Z)-Enoic Acid has Vasodilator Properties in Mesenteric Vessels

Abstract

There is now overwhelming evidence for Epoxyeicosatrienoic acids (EETs) as endothelial derived hyperpolarising factor (EDHF). Most recently, a number of pharmacological tools have been developed for the study of EETs in relation to EDHF responses. EETs have been shown to cause relaxation by activating smooth muscle large conductance Ca2+ sensitive K+ (BKCa) (Archer et al, 2003). This dilatory response has been shown to be specifically inhibited by its analogue 14, 15-epoxyeicosa-5 (Z) enoic acid (14, 15 EEZE) in both human internal mammary artery and bovine coronary artery (Archer et al, 2003). Here we have investigated the antagonist effects of 14, 15 EEZE in murine arteries. Male Black 6 mice (12-18 weeks) were killed by lethal exposure to CO2. First order arteries were isolated and mounted in wire myographs immersed in physiological salt solution (PSS). Arteries were equilibrated (30 mins) and tensions normalised as described previously (Mulvany and Halpern, 1977). Arteries incubated for 30 minutes with or without 3µg/ml 14, 15 EEZE. A concentration response curve to 11, 12 EET was performed cumulatively on arteries pre-contracted with EC80 U46619. In some experiments, arteries were pre-contracted with EC80 U46619, and concentration response to 14, 15 EEZE performed cumulatively.