Long-Term Vardenafil Therapy Improves Hemodynamics in Patients with Pulmonary Hypertension

Aizawa, Katsuo; Hanaoka, Takeshi; Kasai, Hajime; Kurisu, Kaoru; Kumazaki, Setsuo; Koyama, Jun; Tsutsui, Hiroshi; Yazaki, Yoshikazu; Watanabe, Noboru; Katoh, Osamu; Ikeda, Uichi

doi:10.1291/hypres.29.123

Cited by 30 publications

(23 citation statements)

References 32 publications

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“…In some clinical studies it is reported that the clinical efficacy of treatment with sildenafil monotherapy or combination therapy in patients with pulmonary hypertension [40,41]. We need to perform additional studies treated with higher dose of sildenafil in monocrotaline-induced pulmonary hypertensive rats, including new phosphodiesterase type V inhibitors, tadalafil [42] and valdenafil [43]. Further experiments using additional doses of sildenafil and comparison of properties with other phosphoesterase inhibitors would help to clarify this issue.…”

Section: Discussionmentioning

confidence: 99%

3-Hydroxy-3-Methylglutaryl-COA Reductase Inhibitors and Phosphodiesterase Type V Inhibitors Attenuate Right Ventricular Pressure and Remodeling in a Rat Model of Pulmonary Hypertension

Satoh

Satoh²

2009

J Pharm Pharm Sci

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-Purpose. We examined the inhibitory effects of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, a prostacyclin analogue and a phosphodiesterase type V inhibitor on hemodynamic function and cardiac remodeling in rats with monocrotaline-induced pulmonary hypertension. Methods. The rat model of pulmonary hypertension was created by administration of monocrotaline (70 mg/kg, s.c.) to male Wistar rats. A polyethylene tube was introduced into a left carotid artery for measurement of mean arterial pressure (MAP), another into the right ventricle via the right jugular vein for measurement of right ventricular systolic pressure (RVSP).Results. Repeated administration of atorvastatin (2 mg/kg/day, p.o. 0 -28 days) and simvastatin (2 mg/kg/day, p.o. 0 -28 days) significantly reduced RVSP and right ventricular weight (RV)/left ventricular + septum weight (LV + S) without a change in MAP and heart rate. However, repeated administration of pravastatin (4 mg/kg/day, p.o. 0 -28 days) did not reduce the monocrotaline-induced elevation of RVSP and RV/(LV + S) significantly. The reduction of RVSP and RV/(LV + S) induced by a combination of a prostacyclin analogue, beraprost (100 µg/kg/day, 0 -28 days) and simvastatin (2 mg/kg/day, 0 -28 days), was more potent than the effect induced by each drug alone. Sildenafil (5 mg/kg/day, 0 -28 days) tended to reduce RVSP and RV/(LV + S). Repeated combined administration of atorvastatin (2 mg/kg/day, p.o. 0 -28 days) + sildenafil (5 mg/kg/day, p.o. 0 -28 days) significantly reduced lung/body weight. Conclusion. Our present results suggest that repeated administration of the lipophilic HMG-CoA reductase inhibitors, atorvastatin and simvastatin, selectively attenuates the elevation of RVSP, development of pulmonary hypertension and right ventricular remodeling in rats with monocrotaline-induced pulmonary hypertension, and that a combination of HMG-CoA reductase inhibitor and beraprost has a more potent effect than each agent alone. Although the significant inhibitory effect of sildenafil (5mg/kg/day) alone were not observed, higher dosage of sildenafil might attenuate the elevation of RVSP, development of pulmonary hypertension and right ventricular remodeling in rats with monocrotaline-induced pulmonary hypertension. INTRODUCTIONPulmonary hypertension is a serious disease, characterized by progressive elevation of pulmonary arterial resistance, leading to right ventricular failure and death [1]. Although the causes of this disorder are complicated, abnormal vasoconstriction by vascular endothelial injury in pulmonary arterioles, smooth muscle cell proliferation and hypertrophy, contraction of arterioles and remodeling appear to be primary factors. It is reported that release of the vasodilators prostacyclin [2] and nitric oxide [3] decreases, on the other hand, the release of the vasoconstrictor thromboxane A 2 [4] and the expression of endothelin-1 from vascular endothelial cells [5] increases. Therefore, a prostacyclin analogue, epoprostenol, has been administered by cont...

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Section: Discussionmentioning

confidence: 99%

3-Hydroxy-3-Methylglutaryl-COA Reductase Inhibitors and Phosphodiesterase Type V Inhibitors Attenuate Right Ventricular Pressure and Remodeling in a Rat Model of Pulmonary Hypertension

Satoh

Satoh²

2009

J Pharm Pharm Sci

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“…Ghofrani et al 51 demonstrated the importance of studying each drug's specific effect on cardiovascular diseases, given their differences on various hemodynamic parameters. Aizawa et al 52 confirmed Ghofrani et al's 51 finding that vardenafil is not specific to the pulmonary vasculature in the acute setting, but with chronic treatment, only the pulmonary artery pressure and PVR were decreased. The case studies have demonstrated the potential role of tadalafil in patients with severe pulmonary hypertension.…”

Section: Role Of Pde-5 Inhibitors In Pulmonary Hypertensionmentioning

confidence: 63%

“…Aizawa et al 52 Vardenafil decreased both PVR and SVR acutely; chronic treatment reduced PVR/SVR ratio in patients with pulmonary hypertension, suggesting a greater effect on PVR.…”

Section: Study Findingsmentioning

confidence: 99%

Erectile dysfunction and heart failure: the role of phosphodiesterase type 5 inhibitors

Al-Ameri

Kloner

2009

Int J Impot Res

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The phosphodiesterase type 5 (PDE-5) inhibitors are effective in treating erectile dysfunction (ED). ED and heart failure (HF) share similar risk factors, and commonly present together. This association has led to questions ranging from the safety and efficacy of PDE-5 inhibitors in HF patients to a possible role for this class of medication to treat HF patients with or without ED. In addition to endothelial dysfunction, there are causes of ED specific to patients with HF including low exercise tolerance, depression and HF medications. Before treating HF patients with PDE-5 inhibitors, patients should be assessed for their risk of a cardiac event during sexual activity. PDE-5 inhibitors are safe and effective in treating ED in HF patients. An improvement in erectile function by PDE-5 inhibitors was associated with an improvement in quality of life and reduction in depression. Several studies demonstrated the effect of PDE-5 inhibitors on HF per se. PDE-5 inhibitors improved endothelial dysfunction, increased exercise tolerance, decreased pulmonary vascular resistance and pulmonary artery pressure, and increased cardiac index. Several mechanisms whereby PDE-5 inhibitors improve HF have been proposed. PDE-5 inhibitors already have a role in treating primary pulmonary hypertension; however additional studies are needed to determine if they will become a standard therapy for HF patients.

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“…Beş hastadan oluşan seride hastalara 3 ay boyunca günde 3 defa 5 mg vardenafil verilmiş, üçüncü ayda pulmoner arter basıncı ve pulmoner vasküler direncin anlamlı olarak düştüğü görülmüştür. Dünya sağlık örgütü fonksiyonel sınıfı düzelmiş, 6 dakika yürüme testinde değişiklik olmamıştır (10).…”

Section: Vardenafilunclassified

Phosphodiesterase type 5 inhibitors in the treatment of pulmonary arterial hypertension

Kılıçkesmez

Küçükoğlu²

2010

Anadolu Kardiyol Derg

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The pathology of pulmonary arterial hypertension (PAH) is characterized by vascular vasoconstriction, smooth muscle cell proliferation, and thrombosis. Experimental studies have shown the beneficial effect of phosphodiesterase type 5 (PDE-5) inhibitors on pulmonary vascular remodeling and vasodilatation. Randomized clinical trials in monotherapy or combination therapy have been conducted in PAH with sildenafil and tadalafil which significantly improve clinical status, exercise capacity and hemodynamics of PAH patients. Combination therapy of PDE-5 inhibitors with prostacyclin analogs and endothelin receptor antagonists may be helpful in management of PAH. The third PDE-5 inhibitor, vardenafil, is currently being investigated in PAH. Side effects are usually mild and transient and include headache, flushing, nasal congestion, digestive disorders, and myalgia. (

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Long-Term Vardenafil Therapy Improves Hemodynamics in Patients with Pulmonary Hypertension

Cited by 30 publications

References 32 publications

3-Hydroxy-3-Methylglutaryl-COA Reductase Inhibitors and Phosphodiesterase Type V Inhibitors Attenuate Right Ventricular Pressure and Remodeling in a Rat Model of Pulmonary Hypertension

3-Hydroxy-3-Methylglutaryl-COA Reductase Inhibitors and Phosphodiesterase Type V Inhibitors Attenuate Right Ventricular Pressure and Remodeling in a Rat Model of Pulmonary Hypertension

Erectile dysfunction and heart failure: the role of phosphodiesterase type 5 inhibitors

Phosphodiesterase type 5 inhibitors in the treatment of pulmonary arterial hypertension

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