The vasoconstrictor activities of prostaglandin D2 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

Abstract

Prostaglandin (PG) D₂, 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 TxA₂; TP) and/or E prostanoid receptor-3 (one of the vasoconstrictor receptors of PGE₂; 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 PGD₂ 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 PGD₂ 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 PGD₂ 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 PGD₂-evoked depressor response in TP^-/-/EP3^-/- mice as well. These results thus demonstrate that like other PGs, PGD₂ 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.

Keywords: Blood pressure; Prostanoid; Prostanoid receptor; Vasoconstriction.