Stimulation of prostacyclin synthesis by thromboxane A2-like prostaglandin endoperoxide analogues in cultured vascular smooth muscle cells.

In this study, the ability of two chemically stable thromboxane A2-like PG endoperoxide analogues, 15S-hydroxy-9 alpha,11 alpha-(epoxymethano)-prosta-5Z,13E-dienoic acid and 15S-hydroxy-11 alpha,9 alpha-(epoxymethano)-prosta-5Z,13E-dienoic acid, to stimulate PGI2 synthesis by cultured vascular smooth muscle cells isolated from rat superior mesenteric arteries was evaluated. The aforementioned analogues, at concentrations of 0.1 to 10 micrograms/ml, stimulated PGI2 synthesis by 1.5 to 3 fold over basal synthesis. Evoked PGI2 synthesis was essentially over within 2 to 3 min of incubation, similar to previous findings made in vascular smooth muscle cells incubated with peptide hormones, vasopressin and angiotensin II. The PG-stimulatory activity of 15S-hydroxy-9 alpha,11 alpha-(epoxymethano)-prosta-5Z-13E-dienoic acid appeared to be receptor-mediated inasmuch as it was completely inhibited by (+/-)5-endo-(6'-carboxyhex-2'Z-enyl)-6-exo-[1''-[N- (phenylthiocarbamoyl)-hydrazono]-ethyl]-bicyclo[2,2,1] heptane, a novel antagonist of PG endoperoxide analogue-provoked smooth muscle contraction and platelet aggregation. The results suggest that thromboxane A2 and/or PG endoperoxide may stimulate PGI2 synthesis in vascular smooth muscle by a direct, receptor-mediated, interaction.