Kyosuke Sato

Selective and potent inhibitory effect of docosahexaenoic acid (DHA) on U46619-induced contraction in rat aorta

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 Nω-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 inhibitory potencies against prostanoid receptor-mediated contractions, they had a more potent inhibition against TXA2 receptor (TP receptor)-mediated contractions than against PGF2α 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.

Pharmacological characteristics of the inhibitory effects of docosahexaenoic acid on vascular contractions studied in rat mesenteric artery.

Background/Aims: Effects of docosahexaenoic acid (DHA) on blood vessel contractions to various constrictors were investigated in rat mesenteric artery and compared with those of eicosapentaenoic acid (EPA) and linoleic acid (LA). Methods: Tension changes in mesenteric ring segments were isometrically recorded. Results: On sustained contractions induced by a thromboxane A2 mimetic (U46619), DHA exerted a strong inhibitory effect. This inhibitory effect of DHA on U46619 appeared both in endothelium-intact and endothelium-denuded preparations. Although the inhibitory effect of DHA on prostaglandin F2α (PGF2α)-induced contractions was also significant, contractions to phenylephrine (PE) and high-KCI were not affected by DHA. As well as DHA, EPA strongly diminished U46619- and PGF2α-induced contractions without showing a substantial inhibition of PE- and high-KCl-induced contractions. By contrast, LA did not show any significant inhibitory effects on any contractions. The DHA-induced inhibitory actions exerted on U46619 and PGF2α also emerged if ring preparations were pretreated with this ω-3 polyunsaturated fatty acid (PUFA). Conclusion: DHA and EPA are found to more pronouncedly inhibit prostanoid receptor-mediated contractions than other constrictor responses of the mesenteric artery via endothelium-independent mechanisms. These inhibitory effects of ω-3 PUFAs on prostanoid receptor-mediated contractions may partly underlie the mechanisms by which these ω-3 PUFAs elicit protective actions against circulatory disorders.

Acute Effects of Intravenous Administration of Polyunsaturated Fatty Acids on Blood Pressure and Heart Rate in U46619- and Noradrenaline-infused Rats

Experimental studies and epidemiological surveys have indicated that chronic oral administration of the n-3 polyunsaturated fatty acids (PUFAs) docosahexaenoic (DHA) or eicosapentaenoic (EPA) acids reduces blood pressure in hypertensive patients. However, few reports have described the acute blood pressure lowering effects of these PUFAs. In this study, we determined the acute effects of DHA and EPA on blood pressure of rats with increased blood pressure resulting from continuous injection of pressor substances. U46619 (a TXA2 receptor agonist) and noradrenaline (NA) were continuously infused (500 μg/kg/h each) into urethane-anesthetized male Wistar rats and produced sustained elevated mean blood pressure (MBP). In both U46619and NA-infused rats, bolus administration of DHA (3–30 mg/kg, i.v.) reduced blood pressure in a dose-dependent manner, although the MBP reduction was greater in U46619-infused rats. Similarly, administration Original Research Article Chino et al.; BJPR, 15(3): 1-12, 2017; Article no.BJPR.32604 2 of EPA (3–30 mg/kg, i.v.) also induced a greater reduction in MBP of U46619-infused rats. In contrast, bolus administration of linoleic acid (3–30 mg/kg, i.v.), an n-3 type unsaturated fatty acid, failed to reduce blood pressure in all drug-infused rats. Finally, administration of the nitric oxide donor sodium nitroprusside (0.3–100 μg/kg, i.v.) showed a similar blood pressure drop in all druginfused rats. These findings clearly indicate that both DHA and EPA induce acute blood pressure reduction in anesthetized rats, and suggest that the blood pressure drop is mediated via the TXA2 receptor. These characteristic blood pressure lowering effects of these PUFAs are likely to be useful for prevention and treatment of hypertension.