Docosahexaenoic acid inhibits U46619- and prostaglandin F 2α -induced pig coronary and basilar artery contractions by inhibiting prostanoid TP receptors

Docosahexaenoic acid (DHA, an n-3 polyunsaturated fatty acid) inhibits U46619 (a TP receptor agonist)- and prostaglandin F -induced contractions in rat aorta and mesenteric arteries. However, whether these effects could be replicated in vasospasm-prone vessels, such as coronary and cerebral arteries, remains unknown. Here, we evaluated the changes in pig coronary and basilar artery tensions and intracellular Ca concentrations in human prostanoid TP or FP receptor-expressing cells. We aimed to clarify whether DHA inhibits U46619- and prostaglandin F -induced contractions in spasm-prone blood vessels and determine if the TP receptor is the primary target for DHA. In both pig coronary and basilar arteries, DHA suppressed U46619- and prostaglandin F -induced sustained contractions in a concentration-dependent manner, but did not affect contractions induced by 80 mM KCl. SQ 29,548 (a TP receptor antagonist) suppressed U46619- and prostaglandin F -induced contractions by approximately 100% and 60%, respectively. DHA suppressed both U46619- and prostaglandin F induced increases in intracellular Ca concentrations in human TP receptor-expressing cells. However, DHA did not affect prostaglandin F induced increases in intracellular Ca concentrations in human FP receptor-expressing cells. These findings suggest that DHA potently inhibits TP receptor-mediated contractions in pig coronary and basilar arteries, and the primary mechanism underlying its inhibitory effects on arterial contractions involves inhibiting TP receptors.