Treprostinil (TRE) is a potent pulmonary vasodilator with effects on other pathological aspects of pulmonary arterial hypertension. In this study, the prostanoid receptors involved in TRE-induced relaxation of isolated rat pulmonary arteries and TRE-induced inhibition of increased gene expression in collagen synthesis and contractility of human lung fibroblasts were determined. TRE (0.01−100 μM) relaxed prostaglandin F_2α-precontracted rat pulmonary arteries which was attenuated by denudation of the vascular endothelium. TRE-induced relaxation was predominantly blocked by the IP receptor antagonist RO3244194 (1 μM), with slightly greater inhibition in endothelium-denuded tissue. At higher TRE concentrations (> 1 μM), the DP₁ receptor antagonist BW A868C (1 μM) also inhibited relaxation reaching significance above 10 μM. In contrast, the EP₃ receptor antagonist L798106 (1 μM) accentuated TRE-induced relaxation of pulmonary arteries with intact endothelium. In human lung fibroblasts, the EP₂ receptor antagonist PF-04418948 (1 μM) blocked transforming growth factor β1 (TGF-β1)-increased expression of collagen synthesis (COL1A1 and COL1A2) and fibroblast contractility (ACTG2) genes in presence of TRE (0.1 μM). In conclusion, the IP receptor located on rat pulmonary vascular smooth muscle and endothelium is the primary receptor mediating vasorelaxation, while the DP₁ receptor present on the rat endothelium is involved only at higher TRE concentrations. In human lung fibroblasts, the EP₂ receptor is the dominant receptor subtype involved in suppression of increased collagen synthesis and fibroblast contractility gene expression induced by TGF-β1 in the presence of TRE.

曲前列环素 (TRE) 是一种有效的肺血管扩张剂，对肺动脉高压的其他病理方面有影响。在本研究中，确定了参与 TRE 诱导的离体大鼠肺动脉舒张的前列腺素受体，以及 TRE 诱导的对胶原蛋白合成和人肺成纤维细胞收缩性基因表达增加的抑制。 TRE (0.01−100 μM) 松弛前列腺素 F _2α预收缩的大鼠肺动脉，该肺动脉因血管内皮剥脱而减弱。 TRE 诱导的松弛主要被 IP 受体拮抗剂 RO3244194 (1 μM) 阻断，在内皮剥脱组织中的抑制作用稍强。在较高 TRE 浓度 (> 1 μM) 下，DP ₁受体拮抗剂 BWA868C (1 μM) 也能抑制松弛，在 10 μM 以上达到显着效果。相比之下，EP ₃受体拮抗剂 L798106 (1 μM) 增强了 TRE 诱导的具有完整内皮的肺动脉松弛。在人肺成纤维细胞中，EP ₂受体拮抗剂 PF-04418948 (1 μM) 在 TRE 存在的情况下阻断转化生长因子 β1 (TGF-β1) 增加的胶原蛋白合成（ COL1A1和COL1A2 ）和成纤维细胞收缩性 ( ACTG2 ) 基因的表达。 0.1μM）。总之，位于大鼠肺血管平滑肌和内皮上的IP受体是介导血管舒张的主要受体，而存在于大鼠内皮上的DP ₁受体仅在较高TRE浓度下参与。 在人肺成纤维细胞中，EP ₂受体是主要受体亚型，参与抑制 TRE 存在下 TGF-β1 诱导的胶原合成增加和成纤维细胞收缩性基因表达。