Docosahexaenoic acid inhibits U46619- and prostaglandin F2α-induced pig coronary and basilar artery contractions by inhibiting prostanoid TP receptors

Docosahexaenoic acid and eicosapentaenoic acid strongly inhibit prostanoid TP receptor‐dependent contractions of guinea pig gastric fundus smooth muscle

“…To date, we have reported that DHA and EPA very strongly suppress the contractions induced by PGF 2α and U46619 in guinea pig aorta, 8 rat aorta, 9 rat mesenteric arteries, 10 and porcine coronary and basilar arteries 11 . In addition, we found in the present study that DHA and EPA show immediate inhibitory effects against PGA 2 , PGD 2 , PGE 2 , and PGI 2 .…”

“…Although the mechanisms by which DHA and EPA exert preventive effects on these diseases have not been fully elucidated, the suppression of contractile prostanoid production resulting from long‐term ingestion of these n −3 PUFAs is suggested to play an important role in their cardiovascular protection 7 . In contrast, we found that DHA and EPA selectively suppressed blood vessel contractions induced by U46619 (a thromboxane A 2 [TXA 2 ] mimetic) and prostaglandin F 2α (PGF 2α ), which suggests that direct and immediate inhibition by DHA and EPA against prostanoid‐induced vascular contractions partly accounts for their protective effects 8–11 …”

“…We recently found that DHA strongly suppresses U46619‐/PGF 2α ‐induced contractions in pig coronary and basilar arteries and U46619‐/PGF 2α ‐induced increases in Ca 2+ concentrations in TP receptor‐expressing cells, suggesting that the TP receptor is a primary target for DHA. 11 Therefore, in this study, to clarify the degree to which TP receptors contribute to the contractions induced by the five tested prostanoids (PGA 2 , PGD 2 , PGE 2 , PGF 2α , and PGI 2 ) and U46619, the inhibitory effects of SQ 29,548 (a TP receptor antagonist) against these contractions were examined and compared with the suppression exhibited by DHA, EPA, and LA (Figure 6 ). The results suggest that the DHA‐induced inhibitory effects against the GFSM contractions induced by the five tested prostanoids and U46619 were partly but substantially correlated with the inhibitory effect of SQ 29,548 ( r = .08, r 2 = .63) (Figure 6A a).…”

“… 7 In contrast, we found that DHA and EPA selectively suppressed blood vessel contractions induced by U46619 (a thromboxane A 2 [TXA 2 ] mimetic) and prostaglandin F 2α (PGF 2α ), which suggests that direct and immediate inhibition by DHA and EPA against prostanoid‐induced vascular contractions partly accounts for their protective effects. 8 , 9 , 10 , 11 …”

“…7 In contrast, we found that DHA and EPA selectively suppressed blood vessel contractions induced by U46619 (a thromboxane A 2 [TXA 2 ] mimetic) and prostaglandin F 2α (PGF 2α ), which suggests that direct and immediate inhibition by DHA and EPA against prostanoidinduced vascular contractions partly accounts for their protective effects. [8][9][10][11] Prostanoids play important roles in the regulation of contractile responses not only in tonic muscles, such as blood vessels, but also in phasic muscles, including the gastrointestinal tract. For example, various prostanoids and a prostanoid mimetic (U46619) have been reported to produce gastric fundus smooth muscle (GFSM) contractions in experimental animals and humans, namely prostaglandin D 2 (PGD 2 ), prostaglandin E 2 (PGE 2 ), PGF 2α , prostaglandin I 2 (PGI 2 ), 12 and U46619 13 in mice; PGE 2 , 14 PGF 2α , 15 PGI 2 , 16 and U46619 17 in guinea pigs; prostaglandin A 2 (PGA 2 ), 18 PGD 2 , 19 PGE 2 , PGF 2α , PGI 2 , 20 and U46619 21 in rats; and PGD 2 , PGE 2 , PGF 2α , and U46619 22 in humans.…”