Effect of 14,15-epoxyeicosatrienoic acid infusion on blood pressure in normal and hypertensive rats

Intravenous (IV) and intraarterial (IA) infusion of 14,15-epoxyeicosatrienoic acid (14,15-EET) produced a dose-dependent decrease in mean arterial blood pressure (MAP) in normal and spontaneously hypertensive rats (SHR). The hypotensive effect of 14,15-EET was observed from 1μg/kg to 10μg/kg with a maximum reduction in MAP as much as 45±6 mmHg in both normal and SHR. In normal rats the hypotensive effect was found to be more pronounced when 14,15-EET was infused IA than IV. This suggests that 14,15-EET may be metabolized as it passes through the lungs. However, in SHR there was no difference in MAP when 14,15-EET was infused either IA or IV. This indicates that there is a differential removal of the epoxide across the pulmonary circulation. Administration of indomethacin failed to inhibit the hypotensive action of 14,15-EET, suggesting that it may not be a cyclo-oxygenase dependent mechanism. However, the PAF antagonist of BN-52021 inhibited the hypotensive action of 14,15-EET. This therefore, suggests that the release of PAF may be involved in the hypotensive action of this epoxide of arachidonic acid.