Tadalafil, a Long-Acting Inhibitor of PDE5, Improves Pulmonary Hemodynamics and Survival Rate of Monocrotaline-Induced Pulmonary Artery Hypertension in Rats
The aim of this study was to assess the effect of tadalafil (0.5, 2.5, and 10 mg/kg per day) on the progression of pulmonary arterial hypertension (PAH) in early treatment and on the survival rate in late treatment on the monocrotaline (MCT)-induced PAH rat model. Tadalafil was administered once dai...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2009-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319310898 |
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| author | Fusae Sawamura Masami Kato Kazuhisa Fujita Takahiro Nakazawa Anthony Beardsworth |
| author_facet | Fusae Sawamura Masami Kato Kazuhisa Fujita Takahiro Nakazawa Anthony Beardsworth |
| author_sort | Fusae Sawamura |
| collection | DOAJ |
| description | The aim of this study was to assess the effect of tadalafil (0.5, 2.5, and 10 mg/kg per day) on the progression of pulmonary arterial hypertension (PAH) in early treatment and on the survival rate in late treatment on the monocrotaline (MCT)-induced PAH rat model. Tadalafil was administered once daily to rats for 3 weeks from the day of MCT-injection or 21 days after the injection. With early treatment, tadalafil at 10 mg/kg per day prevented the development of PAH by maintaining mean pulmonary artery pressure within the normal range and attenuated right ventricular hypertrophy. With late treatment, tadalafil tended to increase the partial pressure of oxygen in arterial blood and dose-dependently improved the survival rate by 55%, 60%, and 70% at 0.5, 2.5, and 10 mg/kg per day, respectively, versus 40% in the MCT-control group. Both early and late treatments with tadalafil were associated with elevated lung cyclic guanosine monophosphate (cGMP). These results suggest that tadalafil relaxes pulmonary arteries by elevating cGMP in lungs and extend survival time by improving pulmonary hemodynamics even when treatment occurs in the late phase of PAH. Thus, it is expected that tadalafil may be an effective, once-daily treatment option in humans with PAH. Keywords:: tadalafil, phosphodiesterase 5 (PDE5) inhibitor, pulmonary artery hypertension (PAH), monocrotaline (MCT), survival |
| first_indexed | 2024-12-13T14:01:13Z |
| format | Article |
| id | doaj.art-32f41682c9cd49678761e2ce0c12263a |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-13T14:01:13Z |
| publishDate | 2009-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-32f41682c9cd49678761e2ce0c12263a2022-12-21T23:42:43ZengElsevierJournal of Pharmacological Sciences1347-86132009-01-011113235243Tadalafil, a Long-Acting Inhibitor of PDE5, Improves Pulmonary Hemodynamics and Survival Rate of Monocrotaline-Induced Pulmonary Artery Hypertension in RatsFusae Sawamura0Masami Kato1Kazuhisa Fujita2Takahiro Nakazawa3Anthony Beardsworth4Lilly Research Laboratories Japan, Eli Lilly Japan K.K., 7-1-5 Isogami-dori, Chuo-ku, Kobe, Hyogo 651-0086, Japan; Corresponding author. sawamura_fusae@lilly.comHashima Laboratory, Nihon Bioresearch Inc., 104, 6-chome, Majima, Fukuju-cho, Hashima, Gifu 501-6251, JapanHashima Laboratory, Nihon Bioresearch Inc., 104, 6-chome, Majima, Fukuju-cho, Hashima, Gifu 501-6251, JapanLilly Research Laboratories Japan, Eli Lilly Japan K.K., 7-1-5 Isogami-dori, Chuo-ku, Kobe, Hyogo 651-0086, JapanCialis Global Development Team, Eli Lilly and Company Ltd., Erl Wood Manor, GU20 6PH, UKThe aim of this study was to assess the effect of tadalafil (0.5, 2.5, and 10 mg/kg per day) on the progression of pulmonary arterial hypertension (PAH) in early treatment and on the survival rate in late treatment on the monocrotaline (MCT)-induced PAH rat model. Tadalafil was administered once daily to rats for 3 weeks from the day of MCT-injection or 21 days after the injection. With early treatment, tadalafil at 10 mg/kg per day prevented the development of PAH by maintaining mean pulmonary artery pressure within the normal range and attenuated right ventricular hypertrophy. With late treatment, tadalafil tended to increase the partial pressure of oxygen in arterial blood and dose-dependently improved the survival rate by 55%, 60%, and 70% at 0.5, 2.5, and 10 mg/kg per day, respectively, versus 40% in the MCT-control group. Both early and late treatments with tadalafil were associated with elevated lung cyclic guanosine monophosphate (cGMP). These results suggest that tadalafil relaxes pulmonary arteries by elevating cGMP in lungs and extend survival time by improving pulmonary hemodynamics even when treatment occurs in the late phase of PAH. Thus, it is expected that tadalafil may be an effective, once-daily treatment option in humans with PAH. Keywords:: tadalafil, phosphodiesterase 5 (PDE5) inhibitor, pulmonary artery hypertension (PAH), monocrotaline (MCT), survivalhttp://www.sciencedirect.com/science/article/pii/S1347861319310898 |
| spellingShingle | Fusae Sawamura Masami Kato Kazuhisa Fujita Takahiro Nakazawa Anthony Beardsworth Tadalafil, a Long-Acting Inhibitor of PDE5, Improves Pulmonary Hemodynamics and Survival Rate of Monocrotaline-Induced Pulmonary Artery Hypertension in Rats Journal of Pharmacological Sciences |
| title | Tadalafil, a Long-Acting Inhibitor of PDE5, Improves Pulmonary Hemodynamics and Survival Rate of Monocrotaline-Induced Pulmonary Artery Hypertension in Rats |
| title_full | Tadalafil, a Long-Acting Inhibitor of PDE5, Improves Pulmonary Hemodynamics and Survival Rate of Monocrotaline-Induced Pulmonary Artery Hypertension in Rats |
| title_fullStr | Tadalafil, a Long-Acting Inhibitor of PDE5, Improves Pulmonary Hemodynamics and Survival Rate of Monocrotaline-Induced Pulmonary Artery Hypertension in Rats |
| title_full_unstemmed | Tadalafil, a Long-Acting Inhibitor of PDE5, Improves Pulmonary Hemodynamics and Survival Rate of Monocrotaline-Induced Pulmonary Artery Hypertension in Rats |
| title_short | Tadalafil, a Long-Acting Inhibitor of PDE5, Improves Pulmonary Hemodynamics and Survival Rate of Monocrotaline-Induced Pulmonary Artery Hypertension in Rats |
| title_sort | tadalafil a long acting inhibitor of pde5 improves pulmonary hemodynamics and survival rate of monocrotaline induced pulmonary artery hypertension in rats |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319310898 |
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