DDCI-01, a novel long acting phospdiesterase-5 inhibitor, attenuated monocrotaline-induced pulmonary hypertension in rats
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 in...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-11-01
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| Series: | Pulmonary Circulation |
| Online Access: | https://doi.org/10.1177/2045894020939842 |
| _version_ | 1811330752864845824 |
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| author | Ailing Li Zhongkai Zhu Yangke He Qian Dong Dianyong Tang Zhongzhu Chen Wei Huang |
| author_facet | Ailing Li Zhongkai Zhu Yangke He Qian Dong Dianyong Tang Zhongzhu Chen Wei Huang |
| author_sort | Ailing Li |
| collection | DOAJ |
| description | 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 P < 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. |
| first_indexed | 2024-04-13T16:08:36Z |
| format | Article |
| id | doaj.art-0ca3262bfe6b4d9b86542bdeb0f4a6bc |
| institution | Directory Open Access Journal |
| issn | 2045-8940 |
| language | English |
| last_indexed | 2024-04-13T16:08:36Z |
| publishDate | 2020-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pulmonary Circulation |
| spelling | doaj.art-0ca3262bfe6b4d9b86542bdeb0f4a6bc2022-12-22T02:40:19ZengWileyPulmonary Circulation2045-89402020-11-011010.1177/2045894020939842DDCI-01, a novel long acting phospdiesterase-5 inhibitor, attenuated monocrotaline-induced pulmonary hypertension in ratsAiling Li0Zhongkai Zhu1Yangke He2Qian Dong3Dianyong Tang4Zhongzhu Chen5Wei Huang6Institute of Life Science, Chongqing Medical University, Chongqing, P.R. ChinaInstitute of Life Science, Chongqing Medical University, Chongqing, P.R. ChinaInstitute of Life Science, Chongqing Medical University, Chongqing, P.R. ChinaCardiovascular Laboratory, Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. ChinaInternation Academy of Targeted Therapeutics and Innovation, Chongqing University of Arts and Sciences, Chongqing, P.R. ChinaInternation Academy of Targeted Therapeutics and Innovation, Chongqing University of Arts and Sciences, Chongqing, P.R. ChinaInstitute of Life Science, Chongqing Medical University, Chongqing, P.R. ChinaPulmonary 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 P < 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.https://doi.org/10.1177/2045894020939842 |
| spellingShingle | Ailing Li Zhongkai Zhu Yangke He Qian Dong Dianyong Tang Zhongzhu Chen Wei Huang DDCI-01, a novel long acting phospdiesterase-5 inhibitor, attenuated monocrotaline-induced pulmonary hypertension in rats Pulmonary Circulation |
| title | DDCI-01, a novel long acting phospdiesterase-5 inhibitor, attenuated monocrotaline-induced pulmonary hypertension in rats |
| title_full | DDCI-01, a novel long acting phospdiesterase-5 inhibitor, attenuated monocrotaline-induced pulmonary hypertension in rats |
| title_fullStr | DDCI-01, a novel long acting phospdiesterase-5 inhibitor, attenuated monocrotaline-induced pulmonary hypertension in rats |
| title_full_unstemmed | DDCI-01, a novel long acting phospdiesterase-5 inhibitor, attenuated monocrotaline-induced pulmonary hypertension in rats |
| title_short | DDCI-01, a novel long acting phospdiesterase-5 inhibitor, attenuated monocrotaline-induced pulmonary hypertension in rats |
| title_sort | ddci 01 a novel long acting phospdiesterase 5 inhibitor attenuated monocrotaline induced pulmonary hypertension in rats |
| url | https://doi.org/10.1177/2045894020939842 |
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