The vasoconstrictor activities of prostaglandin D via the thromboxane prostanoid receptor and E prostanoid receptor-3 outweigh its concurrent vasodepressor effect mainly through D prostanoid receptor-1 ex vivo and in vivo.

Prostaglandin (PG) D, a commonly considered vasodilator through D prostanoid receptor-1 (DP1), might also evoke vasoconstriction via acting on the thromboxane (Tx)-prostanoid receptor (the original receptor of TxA; TP) and/or E prostanoid receptor-3 (one of the vasoconstrictor receptors of PGE; EP3). This study aimed to test the above hypothesis in the mouse renal vascular bed (main renal arteries and perfused kidneys) and/or mesenteric resistance arteries and determine how the vasoconstrictor mechanism influences the overall PGD effect on systemic blood pressure under in vivo conditions. Experiments were performed on control wild-type (WT) mice and mice with deficiencies in TP (TP) and/or EP3 (EP3). Here we show that PGD indeed evoked vasoconstrictor responses in the above-mentioned tissues of WT mice, which were however not only reduced by TP or EP3, but also reversed by TP/EP3 in some of the above tissues (mesenteric resistance arteries or perfused kidneys) to dilator reactions that were reduced by non-selective DP antagonism. A slight or mild pressor response was also observed with PGD under in vivo conditions, and this was again reversed to a depressor response in TP or TP/EP3 mice. Non-selective DP antagonism reduced the PGD-evoked depressor response in TP/EP3 mice as well. These results thus demonstrate that like other PGs, PGD activates TP and/or EP3 to evoke vasoconstrictor activities, which can outweigh its concurrent vasodepressor activity mediated mainly through DP1, and hence result in a pressor response, although the response might only be of a slight or mild extent.