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© Copyright 2004 The British Pharmacological Society

036P University of Bath
Summer Meeting July 2004

14, 15 epoxyeicosa-5(Z)-enoic acid has vasodilator properties in mesenteric vessels

Louise S. Harrington, John R. Falck* and Jane A. Mitchell. Cardiothoracic Pharmacology, Unit of Critical Care Medicine, The National Heart and Lung Institute, Imperial College, Dovehouse Street, London, SW3 6LY, UK. * Dept. of Biochemistry, UT Southwestern medical centre, Texas 75390-9038, USA

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Harrington LS
Falck JR
Mitchell JA

There is now overwhelming evidence supporting a role for epoxyeicosatrienoic acids (EETs) as endothelial derived hyperpolarising factors (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 can be specifically inhibited by the analogue 14, 15-epoxyeicosa-5 (Z) enoic acid (14, 15 EEZE) in both human and bovine vessels (Archer et al, 2003, Gauthier et al2002) . Here we have investigated the effects of 14, 15 EEZE on vasomotor responses 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 10-5M14, 15 EEZE. Increasing concentrations of 11, 12 EET were then added in a cumulative fashion to arteries pre-contracted with U46619 (10-8M). In some experiments, increasing concentrations of 14, 15 EEZE were added to U46619-precontracted arteries.

Figure 1: Vasodilator effects of 11, 12 EET are inhibited by pre-incubation with 10--5M 14, 15 EEZE. Figure 2: Vasodilatory effects of 14, 15 EEZE in U46619 pre-contracted arteries. Data is shown as % of U46619 induced tone S.E.M. for n=4-5 experiments.

Here we show that 11, 12 EET is an effective vasodilator of murine mesenteric arteries (figure 1), which can be inhibited by the structural analogue and antagonist 14, 15 EEZE. However, 14, 15 EEZE is, itself, an effective vasodilator (figure 2), The possibility remains form 14,15 EEZE to act as a partial agonist for the EET/EDHF receptor. These results illustrate an important pharmacological property of14,15 EEZE which should be considered when used in the study of EDHF.

Archer SL et al (2003). Circulation 107:769-776
Gauthier KM et al(2002). Circ. Res. 90:1028-1036
Mulvany MJ and Halpern W (1977) Circ.Res. 41:19-26

The work was supported by the BHF