title: Selective and potent inhibitory effect of docosahexaenoic acid (DHA) on U46619-induced contraction in rat aorta.
abstract: 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 TXA(2) 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 PGF(2α)-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 PGF(2α) 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 PGF(2α). 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 inhibitory potencies against prostanoid receptor-mediated contractions, they had a more potent inhibition against TXA(2) receptor (TP receptor)-mediated contractions than against PGF(2α) receptor (FP receptor)-mediated responses. Selective inhibition by either DHA or EPA of prostanoid receptor-mediated blood vessel contractions may partly underlie the mechanisms by which these ω-3 polyunsaturated fatty acids exert their circulatory-protective effects.
authors.affiliation: Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Sato
authors.forename: Daisuke
authors.initials: D
authors.lastname: Chino
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Obara
authors.forename: Seiji
authors.initials: S
authors.lastname: Miyauchi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D015237:Dinoprost / Q000037:antagonists & inhibitors; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D019787:Linoleic Acid / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D044244:Receptors, Thromboxane A2, Prostaglandin H2; D014662:Vasoconstrictor Agents; D004281:Docosahexaenoic Acids; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019787:Linoleic Acid; D015118:Eicosapentaenoic Acid; D015237:Dinoprost