Selective and potent inhibitory effect of docosahexaenoic acid (DHA) onU46619-induced contraction in rat aorta

摘要

Inhibitory effects of docosahexaenoic acid (DHA) on blood vessel contractions induced by various constrictor stimulants were investigated in the rat thoracic aorta. The inhibitory effects of DHA were also compared with those of eicosapentaenoic acid (EPA) and linoleic acid (LA). DHA exhibited a strong inhibitory effect on the sustained contractions induced by U46619, a TXA2 mimetic. This inhibitory effect of DHA was not affected by removal of the endothelium or by treatment with either indomethacin or N^ω-nitro-l-arginine. DHA also significantly diminished PGF2α-induced contraction but did not show any appreciable inhibitory effects on the contractions to both phenylephrine (PE) and high-KCl. Similarly, EPA exhibited significant inhibitory effects against the contractions induced by both U46619 and PGF2α without substantially affecting either PE- or high-KCl-induced contractions. However, both DHA and EPA generated more potent inhibitions against contractions induced by U46619 than those by PGF2α. In contrast, LA did not show significant inhibitory effects against any contractions, including those induced by U46619. The present findings suggest that DHA and EPA elicit more selective inhibition against blood vessel contractions that are mediated through stimulation of prostanoid receptors than those through α-adrenoceptor stimulation or membrane depolarization. Although DHA and EPA have similar inhibitorypotencies against prostanoid receptor-mediated contractions, they had a more potentinhibition against TXA2 receptor (TP receptor)-mediated contractions thanagainst PGF2α receptor (FP receptor)-mediated responses. Selective inhibitionby either DHA or EPA of prostanoid receptor-mediated blood vessel contractions may partlyunderlie the mechanisms by which these ω-3 polyunsaturated fatty acids exert theircirculatory-protective effects.