No abstract

Eicosapentaenoic acid (EPA) is an n-3 polyunsaturated fatty acid (PUFA) found in fish oil. We recently showed that docosahexaenoic acid (DHA), another n-3 PUFA, potently inhibited pig basilar and coronary artery contractions induced by U46619 (a TP receptor agonist) and prostaglandin (PG) F 2α . We also showed that prostanoid TP receptors are potential targets for DHA. In this study, we investigated whether EPA, like DHA, suppresses contractions of pig basilar and coronary arteries induced by U46619 and PGF 2α through inhibition of the TP receptor.EPA suppressed both U46619-and PGF 2α -induced pig basilar and coronary contractions in a concentrationdependent manner without affecting 80 mM KCl-induced contractions. U46619-/PGF 2α -induced contractions in both arteries were completely/largely suppressed by SQ 29,548 (a TP receptor antagonist). In addition, EPA suppressed U46619-/PGF 2α -induced increases in intracellular Ca 2+ concentrations ([Ca 2+ ] i ) in human TP receptoroverexpressing 293T cells, whereas it showed only a slight effect on PGF 2α -induced [Ca 2+ ] i increases in human FP receptor-overexpressing 293T cells. These findings suggest that EPA strongly suppresses TP-receptor-mediated contractions of pig basilar and coronary arteries, which can be partially attributed to its inhibitory effects on the TP receptor.

This study was performed to elucidate whether eicosapentaenoic acid (EPA) suppresses spasm-prone blood vessel contractions induced by a thromboxane mimetic (U46619) and prostaglandin F2α (PGF2α) and determine whether the primary target of EPA is the prostanoid TP receptor. Accordingly, we assessed: (1) the tension changes in porcine basilar and coronary arteries, and (2) changes in the Fura-2 (an intracellular Ca2+ indicator) fluorescence intensity ratio at 510 nm elicited by 340/380 nm excitation (F340/380) in 293T cells expressing the human TP receptor (TP-293T cells) and those expressing the human prostanoid FP receptor (FP-293T cells). EPA inhibited both porcine basilar and coronary artery contractions induced by U46619 and PGF2α in a concentration-dependent manner, but it did not affect the contractions induced by 80 mM KCl. EPA also inhibited the increase in F340/380 induced by U46619 and PGF2α in TP-293T cells. In contrast, EPA showed only a marginal effect on the increase in F340/380 induced by PGF2α in FP-293T cells. These findings indicate that EPA strongly suppresses the porcine basilar and coronary artery contractions mediated by TP receptor and that inhibition of TP receptors partly underlies the EPA-induced inhibitory effects on these arterial contractions.

DHA is a typical n-3 polyunsaturated fatty acid (n-3 PUFA), and numerous epidemiological and clinical studies have shown that its intake exerts beneficial preventive effects against various cardiovascular diseases. Although possible vascular relaxation induced by DHA seems to be a mechanism underlying its cardioprotective effects, few pharmacological studies have been reported to evidence this idea. In this regard, we found that in the isolated rat thoracic aortae and mesenteric arteries, DHA shows acute and selective suppressive effects against prostanoid receptor-mediated contraction, which may partly underly its cardiovascular protective effects. In this study, we examined the possibility that DHA also shows selective suppressive effects vs. prostanoid receptor-mediated contractions in coronary and cerebral arteries. In both porcine coronary and cerebral arteries, DHA (~3 × 10 −5 M) inhibited U46619-and PGF 2α -induced contractions more potently than high (80 mM)-KCl-induced contraction.These findings suggest that DHA strongly and selectively suppresses prostanoid receptor-mediated contraction in both coronary and cerebral arteries, which suggests that this n-3 PUFA is also significant in preventing the occurrence of coronary and cerebral spasm due to contractile prostaglandins.