Increased role of E prostanoid receptor-3 in prostacyclin-evoked contractile activity of spontaneously hypertensive rat mesenteric resistance arteries.

This study aimed to determine whether E prostanoid receptor-3 (EP3) is involved in prostacyclin (PGI₂)-evoked vasoconstrictor activity of resistance arteries and if so, how it changes under hypertensive conditions. Mesenteric resistance arteries from Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) were isolated for functional and biochemical studies. Here we show that in vessels from WKYs, PGI₂ or the endothelial muscarinic agonist ACh (which stimulates in vitro PGI₂ synthesis) evoked vasoconstrictor activity, which increased in SHRs. The thromboxane-prostanoid receptor (TP) antagonist SQ29548 partially removed the vasoconstrictor activity, and an increased contractile activity of PGI₂ resistant to SQ29548 was observed in SHRs. Interestingly, L798106, an antagonist of EP3 (whose expression was higher in SHRs than in WKYs), not only added to the effect of SQ29548 but also caused relaxation to PGI₂ more than that obtained with SQ29548. In accordance, EP3 deletion, which reduced PGI₂-evoked contraction, together with SQ29548 resulted in relaxation evoked by the agonist in mouse aortas. These results thus demonstrate an explicit involvement of EP3 in PGI₂-evoked vasoconstrictor activity in rat mesenteric resistance arteries and suggest that up-regulation of the receptor contributes significantly to the increased contractile activity evoked by PGI₂ under hypertensive conditions.

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