Although recognized to have an in vivo vasodepressor effect blunted by the vasoconstrictor effect of E-prostanoid receptor-3 (EP3), prostaglandin E 2 (PGE 2 ) evokes contractions of many vascular beds that are sensitive to antagonizing the thromboxane prostanoid receptor (TP). This study aimed to determine the direct effect of PGE 2 on renal arteries and/or the whole renal vasculature and how each of these two receptors is involved in the responses. Experiments were performed on isolated vessels and perfused kidneys of wild-type mice and/or mice with deficiency in TP (TP −/− ), EP3 (EP3 −/− ), or both TP and EP3 (TP −/− /EP3 −/− ). Here we show that PGE 2 (0.001-30 μM) evoked not only contraction of main renal arteries, but also a decrease of flow in perfused kidneys. EP3 -/diminished the response to 0.001-0.3 μM PGE 2 , while TP −/− reduced that to the prostanoid of higher concentrations. In TP −/− /EP3 −/− vessels and perfused kidneys, PGE 2 did not evoke contraction but instead resulted in vasodilator responses. These results demonstrate that PGE 2 functions as an overall direct vasoconstrictor of the mouse renal vasculature with an effect reflecting the vasoconstrictor activities outweighing that of dilation. Also, our results suggest that EP3 dominates the vasoconstrictor effect of PGE 2 of low concentrations (≤0.001-0.3 μM), but its effect is further added by that of TP, which has a higher efficacy, although activated by higher concentrations (from 0.01 μM) of the same prostanoid PGE 2 . K E Y W O R D S EP3, gene deficiency, PGE 2 , renal vasoconstriction, TP | 2569 LIU et aL. How to cite this article: Liu B, Wu X, Zeng R, et al. Prostaglandin E 2 sequentially activates E-prostanoid receptor-3 and thromboxane prostanoid receptor to evoke contraction and increase in resistance of the mouse renal vasculature.

Vasomotor reactions of prostacyclin (prostaglandin I 2 ; PGI 2) can be collectively modulated by thromboxane prostanoid receptor (TP), E-prostanoid receptor-3 (EP3), and the vasodilator I prostanoid receptor (IP). This study aimed to determine the direct effect of PGI 2 on renal arteries and/or the whole renal vasculature and how each of these receptors is involved. Experiments were performed on vessels or perfused kidneys of wild-type mice and/or mice with deficiency in TP (TP −/−) and/ or EP3. Here we show that PGI 2 did not evoke relaxation, but instead resulted in contraction of main renal arteries (from ~0.001-0.01 µM) or reduction of flow in perfused kidneys (from ~1 µM); either of them was reversed into a dilator response in TP −/− /EP3 −/− counterparts. Also, we found that in renal arteries although it has a lesser effect than TP −/− on the maximal contraction to PGI 2 (10 µM), EP3 −/− but not TP −/− resulted in relaxation to the prostanoid at 0.01-1 µM. Meanwhile, TP −/− only significantly reduced the contractile activity evoked by PGI 2 at ≥0.1 µM. These results demonstrate that PGI 2 may evoke an overall vasoconstrictor response in the mouse renal vasculature, reflecting activities of TP and EP3 outweighing that of the vasodilator IP. Also, our results suggest that EP3, on which PGI 2 can have a potency similar to that on IP, plays a major role in the vasoconstrictor effect of the prostanoid of low concentrations (≤1 µM), while TP, on which PGI 2 has a lower potency but higher efficacy, accounts for a larger part of its maximal contractile activity.

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