Prostaglandin E2 sequentially activates E-prostanoid receptor-3 and thromboxane prostanoid receptor to evoke contraction and increase in resistance of the mouse renal vasculature

Abstract

Although recognized to have an in vivo vasodepressor effect blunted by the vasoconstrictor effect of E-prostanoid receptor-3 (EP3), prostaglandin E₂ (PGE₂ ) 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 PGE₂ 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 PGE₂ (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 PGE₂ , while TP^-/- reduced that to the prostanoid of higher concentrations. In TP^-/- /EP3^-/- vessels and perfused kidneys, PGE₂ did not evoke contraction but instead resulted in vasodilator responses. These results demonstrate that PGE₂ 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 PGE₂ 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 PGE₂ .

Keywords: EP3; PGE2; TP; gene deficiency; renal vasoconstriction.