The prostacyclin-mimetic cicaprost inhibits endogenous endothelin-1 release from human pulmonary artery smooth muscle cells

There is increasing evidence supporting a role fur endothelin-1 (ET-1) in h uman pulmonary hypertension. The aim of this study was to determine the rel ative roles of human pulmonary microvascular endothelial cells (HPMVE) and human pulmonary artery smooth muscle (HPASM) cells to produce ET-1 under in flammatory conditions and to investigate further possible control mechanism s of ET-1 production by HPASM. Although HPMVE cells produced more ET-1 than HPASM when cultured with fetal calf serum (FCS) alone and after treatment with cytokines; HPASM produced significant amounts of ET-1 after stimulatio n with cytokines. Cytokine-stimulated increase in ET-1 production by HPASM was inhibited by cicaprost, a prostacyclin analogue, and other agents that are known to increase intracellular cyclic AMP. Cicaprost also inhibited pr oliferation of HPASM in response to FCS lending support to the theory that part of the clinical benefit seen in long-term treatment with prostacyclin in pulmonary hypertension may be a result of inhibition of ET-1 production in these cells.