Differential properties of E prostanoid receptor-3 and thromboxane prostanoid receptor in activation by prostacyclin to evoke vasoconstrictor response in 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 similar to 0.001-0.01 mu M) or reduction of flow in perfused kidneys (from similar to 1 mu M); 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 mu M), EP3(-/-)but not TP(-/-)resulted in relaxation to the prostanoid at 0.01-1 mu M. Meanwhile, TP(-/-)only significantly reduced the contractile activity evoked by PGI(2)at >= 0.1 mu M. 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 mu M), while TP, on which PGI(2)has a lower potency but higher efficacy, accounts for a larger part of its maximal contractile activity.