A comparative study of PGI2 mimetics used clinically on the vasorelaxation of human pulmonary arteries and veins, role of the DP-receptor

Differential actions of the prostacyclin analogues treprostinil and iloprost and the selexipag metabolite, MRE-269 (ACT-333679) in rat small pulmonary arteries and veins

“…These findings are very comparable to those very recently reported on the relaxant activity to treprostinil in human pulmonary arteries compared to human pulmonary veins and the sensitivity of the responses to IP antagonists ( [20] this issue of POLM). In rat pulmonary tissue, the IP receptor antagonists partially inhibited iloprost-induced relaxation of both rat pulmonary arteries and veins, indicating some dependency of this response on the IP receptor, which contrasts to the failure to antagonise the vasorelaxant responses to MRE-269 in either rat pulmonary tissue.…”

“…This conclusion is based on the findings that two selective and structurally unrelated IP receptor antagonists, RO1138452 or RO3244794 [21] could essentially abolish the relaxation to treprostinil. Recently, it has also been reported that IP antagonists can likewise completely inhibit the vasorelaxant responses to treprostinil in the human pulmonary artery [20] (this issue of POLM). The findings in rat tissue with iloprost with the two IP antagonists, suggest that IP receptors appear to be only partially involved with its relaxant action on rat small pulmonary arteries and veins.…”

“…Thus, in addition to their vasodilator IP receptor agonist activity, the preferential binding of iloprost to the vasoconstrictor EP 1 receptor, which contrasts with the binding of treprostinil to the vasodilator DP 1 and EP 2 receptors, is a strong basis for possible differences in their pharmacological profiles [7]. Moreover, using selective prostanoid receptor antagonists, very recent findings using human pulmonary veins suggest roles for both the IP and DP 1 receptor in the vasorelaxant responses to treprostinil [20] (this issue of POLM).…”

Comparative studies of pharmacokinetics and anticoagulatory effect in rats after oral administration of Frankincense and its processed products

“…Content of TAT can be a sensitive measure of body blood coagulation, and it has been used as an important indicator that measures blood coagulation system activity. PGI 2 is one of arachidonic acid metabolites, and it has functions that diastole blood vessels and inhibit platelet aggregation (Benyahia et al, 2013). The present study demonstrated that both FRA and its processed products reduced the levels of D-D and TAT and increased PGI 2 level in cold coagulation and blood stasis model rats, which illustrated that FRA and its processed products promoted blood circulation to remove blood stasis.…”

Prostanoid EP2 Receptors Are Up-Regulated in Human Pulmonary Arterial Hypertension: A Key Anti-Proliferative Target for Treprostinil in Smooth Muscle Cells

“…Prostacyclin and its chemically stable analogues, iloprost and treprostinil, are used extensively in the treatment of PAH [2,3,4]. Early work on prostacyclin or its analogues (the prostacyclins) considered that activity at the prostanoid IP receptor significantly contributed to their pharmacological properties in humans [5], including potent vasodilator effects in the pulmonary vasculature [2,6,7] and anti-proliferative effects in distal pulmonary arterial smooth muscle cells (PASMCs) derived from normal lungs [8,9]. Based on this concept, selexipag, a novel non-prostanoid and highly selective IP receptor agonist was developed for PAH [10,11] and is now a clinically approved treatment [12].…”