Endothelium modulates vasoconstrictor response to prostaglandin I-2 in rat mesenteric resistance arteries: interaction between EP1 and TP receptors

Background and purpose: Prostacyclin (PGI(2)) is usually described as an endothelium-derived vasodilator, but it can also induce vasoconstriction. We studied the vasomotor responses to PGI(2) in resistance arteries and the role of thromboxane (TP) and prostaglandin E-2 (EP) receptors in this effect. Experimental approach: Mesenteric resistance arteries were obtained from Sprague-Dawley rats. Vasomotion to PGI(2) was studied in segments of these arteries with and without endothelium and in presence of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the potassium channel blockers apamin plus charybdotoxin, the non-selective EP receptor antagonist AH6809, the selective TP receptor antagonist SQ29548 or the EP1 receptor antagonist SC19220. PGI(2)-induced NO release was analysed in the absence or presence of SQ29548, AH6809 or SC19220. Key results: PGI(2) caused contractions in arterial segments that were increased by endothelium removal, L-NAME or L-NAME plus apamin plus charybdotoxin and abolished by SQ29548. In segments with endothelium, AH6809 or SC19220 almost abolished the contractions to PGI(2); this effect was prevented by L-NAME, L-NAME plus apamin plus charybdotoxin or by endothelium removal. PGI(2) induced NO release that was inhibited by the prostacyclin receptor (IP receptor) antagonist, RO1138452, and increased by SQ29548, SC19220 and AH6809. The increase in NO release induced by these separate drugs was inhibited by RO1138452. Conclusions and implications: PGI(2) activated the TP receptor in mesenteric resistance arteries and produced vasoconstriction, which the endothelium modulated through TP and EP1 receptors. PGI(2) also released endothelium-derived hyperpolarizing factor and, through IP receptor activation, induced NO release, which in turn, was antagonized by TP and EP1 receptor activation.