Li Ailing, Zhu Zhongkai, He Yangke, Dong Qian, Tang Dianyong, Chen Zhongzhu, Huang Wei
Cardiovascular Laboratory, Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
Institute of Life Science, Chongqing Medical University, Chongqing, P.R. China.
Pulm Circ. 2020 Nov 11;10(4):2045894020939842. doi: 10.1177/2045894020939842. eCollection 2020 Oct-Dec.
Pulmonary arterial hypertension is a progressive, malignant heart disease, characterized by pulmonary arteriole remodeling and increased pulmonary vascular resistance, which eventually leads to right heart failure. This study sought to evaluate the effects of a novel long-acting phospdiesterase-5 inhibitor, namely DDCI-01, as an early intervention for monocrotaline-induced pulmonary hypertensive rats. To establish this model, 50 mg/kg of monocrotaline was intraperitoneally injected into rats. At Day 7 after monocrotaline injection, two doses of DDCI-01 (3 or 9 mg/kg/day) or tadalafil (at 3 or 9 mg/kg/day) were intragastrically administered. The rats were anesthetized with pentobarbital for hemodynamic and echocardiographic measurements, at Day 21 after monocrotaline injection. Compared to the monocrotaline group, DDCI-01 at 3 and 9 mg/kg/day (P) reduced the mean pulmonary arterial pressure (mPAP), right ventricular systolic pressure, right ventricular transverse diameter, pulmonary arterial medial wall thickness (WT%), and right ventricle hypertrophy. However, no significant difference in the indices mentioned as above was found between DDCI-01 (3 mg/kg/day) and tadalafil (3 mg/kg/day). In addition, DDCI-01 at 9 mg/kg/day resulted in lower mPAP and WT%, as well as higher cyclic guanosine monophosphate levels in the lung and plasma compared with the same dose of tadalafil (9 mg/kg/day) (all < 0.05). These findings suggested that DDCI-01 improved monocrotaline-induced pulmonary hypertension in rats, and a dose of DDCI-01 of 9 mg/kg/day might be more effective than the same dose of tadalafil in monocrotaline-induced pulmonary hypertension in rats.
肺动脉高压是一种进行性的恶性心脏病，其特征为肺小动脉重塑和肺血管阻力增加，最终导致右心衰竭。本研究旨在评估新型长效磷酸二酯酶-5抑制剂DDCI-01作为对野百合碱诱导的肺动脉高压大鼠的早期干预措施的效果。为建立该模型，将50mg/kg的野百合碱腹腔注射到大鼠体内。在注射野百合碱后第7天，经胃给予两剂DDCI-01（3或9mg/kg/天）或他达拉非（3或9mg/kg/天）。在注射野百合碱后第21天，用戊巴比妥麻醉大鼠以进行血流动力学和超声心动图测量。与野百合碱组相比，3和9mg/kg/天的DDCI-01降低了平均肺动脉压（mPAP）、右心室收缩压、右心室横径、肺动脉中膜厚度（WT%）和右心室肥大。然而，在DDCI-01（3mg/kg/天）和他达拉非（3mg/kg/天）之间未发现上述指标有显著差异。此外，与相同剂量的他达拉非（9mg/kg/天）相比，9mg/kg/天的DDCI-01导致更低的mPAP和WT%，以及肺和血浆中更高的环磷酸鸟苷水平（均P<0.05）。这些发现表明，DDCI-01改善了野百合碱诱导的大鼠肺动脉高压，并且9mg/kg/天的DDCI-01剂量在野百合碱诱导的大鼠肺动脉高压中可能比相同剂量的他达拉非更有效。
