Endothelium modulates vasoconstrictor response to prostaglandin I2 in rat mesenteric resistance arteries: interaction between EP1 and TP receptors

Background and purpose:

Prostacyclin (PGI₂) is usually described as an endothelium-derived vasodilator, but it can also induce vasoconstriction. We studied the vasomotor responses to PGI₂ in resistance arteries and the role of thromboxane (TP) and prostaglandin E₂ (EP) receptors in this effect.

Experimental approach:

Mesenteric resistance arteries were obtained from Sprague-Dawley rats. Vasomotion to PGI₂ was studied in segments of these arteries with and without endothelium and in presence of the nitric oxide (NO) synthase inhibitor N^G-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. PGI₂-induced NO release was analysed in the absence or presence of SQ29548, AH6809 or SC19220.

Key results:

PGI₂ 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 PGI₂; this effect was prevented by L-NAME, L-NAME plus apamin plus charybdotoxin or by endothelium removal. PGI₂ 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:

PGI₂ activated the TP receptor in mesenteric resistance arteries and produced vasoconstriction, which the endothelium modulated through TP and EP₁ receptors. PGI₂ 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.