DA-8159, a New PDE5 Inhibitor, Attenuates the Development of Compensatory Right Ventricular Hypertrophy in a Rat Model of Pulmonary Hypertension

Kang, Kyung Koo; Ahn, Gook Jun; Sohn, Yong Sung; Ahn, Byoung Ok; Kim, W B

doi:10.1177/147323000303100608

Cited by 15 publications

(12 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a previous study, DA-8159 increased the level of sodium nitroprusside-stimulated relaxation in the cavernosal strips of diabetic rabbits (Kang et al, 2004). Furthermore, it reduced the right ventricular hypertrophy and medial wall thickening in an animal model of monocrotaline-induced pulmonary hypertension (Kang et al, 2003).…”

Section: Introductionmentioning

confidence: 97%

Chronic treatment of DA-8159, a new phosphodiesterase type V inhibitor, attenuates endothelial dysfunction in stroke-prone spontaneously hypertensive rat

2006

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 97%

Chronic treatment of DA-8159, a new phosphodiesterase type V inhibitor, attenuates endothelial dysfunction in stroke-prone spontaneously hypertensive rat

2006

View full text Add to dashboard Cite

“…It is not obvious that PDE 5 inhibitors such as DA-8159 is able to increase the bioavailability of NO preventing the formation of peroxynitrate as a result of nitrosative stress in diabetic rats; our earlier study demonstrated that plasma NO level was increased by long-term administration of DA-8159 in pulmonary hypertensive rats (Kang et al, 2003). Although measurement of NO level and immunohistochemistry for peroxinitrate were not carried out in this study, we suppose that DA-8159 leads to an increase of NO level by enhancing the bioavailability of NO to targeted cells.…”

Section: Discussionmentioning

confidence: 97%

“…It is not obvious that PDE 5 inhibitors such as DA‐8159 is able to increase the bioavailability of NO preventing the formation of peroxynitrate as a result of nitrosative stress in diabetic rats; our earlier study demonstrated that plasma NO level was increased by long‐term administration of DA‐8159 in pulmonary hypertensive rats (Kang et al. , 2003).…”

Section: Discussionmentioning

confidence: 99%

Chronic administration of phosphodiesterase 5 inhibitor improves erectile and endothelial function in a rat model of diabetes

Ahn

Choi

et al. 2005

Int J of Andrology

View full text Add to dashboard Cite

This study was conducted to determine if the long-term administration of the phosphodiesterase type 5 (PDE 5) inhibitor, DA-8159, to diabetic rats can ameliorate the development of erectile dysfunction (ED) and endothelial dysfunction. After inducing diabetes with streptozotocin, DA-8159 was orally administered at a dose of 3 mg/kg or 10 mg/kg for 8 weeks. To examine the effect on erectile response, electrostimulation of the cavernous nerve with the parameters of 3 V, 5 ms, 5 Hz or 10 Hz, was performed to measure the intracavernous pressure (ICP) and mean arterial pressure (MAP). Thoracic aorta relaxation in vitro was evaluated by adding acetylcholine (Ach) cumulatively to the bathing medium. In addition, the plasma endothelin-1 (ET-1) levels were measured in order to investigate the effect of DA-8159 on endothelial dysfunction. The area under the curve (AUC) from the ICP/MAP ratio in the 10 Hz stimulation showed a significantly increased AUC after the 10 mg/kg treatment compared with the diabetic group (8891 +/- 619 vs. 6316 +/- 1016, respectively, p < 0.05). At the 5 Hz frequency, DA-8159 10 mg/kg also induced a significant increase in the AUC compared with the diabetic control. The maximum ICP/MAP ratio (%) of the 10 mg/kg treatment group was significantly higher in both the 10 Hz and 5 Hz frequency groups (p < 0.05). A treatment of 3 mg/kg tended to increase the AUC and peak ICP/MAP but was not statistically significant. The Ach EC50 value of the diabetic group was significantly higher than in the normal control (120.50 +/- 22.90 nm vs. 86.80 +/- 9.30 nm, respectively), and 10 mg/kg treatment group showed a significantly lower EC(50) value (88.38 +/- 19.7 nm). The ET-1 level was lower in groups treated with DA-8159, 3 mg/kg and 10 mg/kg treatment induced a statistical difference compared with the diabetic control (1.15 +/- 0.34 fmol/mL vs. 2.51 +/- 0.55 fmol/mL, respectively, p < 0.05). These results demonstrate that chronic administration of DA-8159 could attenuate the development of the ED in diabetes and its effect is associated with an improvement in the endothelial function.

show abstract

“…Udenafil is similar to sildenafil in molecular structures (Figure 1), and is comparable with sildenafil in terms of PDE5 selectivity and its broad range of safety margin [14]. Furthermore, laboratory data showed that udenafil inhibits ventricular hypertrophy and fibrosis in a rat HF model [15]. In the preclinical study, udenafil increased serum cGMP levels, decreased intracellular Ca 2+ concentrations, and produced vasodilatation.…”

Section: Introductionmentioning

confidence: 99%

ULTIMATE-SHF trial (UdenafiL Therapy to Improve symptoMAtology, exercise Tolerance and hEmodynamics in patients with chronic systolic heart failure): study protocol for a randomized, placebo-controlled, double-blind trial

Kim

Hwang

et al. 2013

Trials

View full text Add to dashboard Cite

BackgroundOver the last few years, the use of phosphodiesterase type 5 (PDE5) inhibitors has been expanded to management of various cardiovascular disorders beyond pulmonary arterial hypertension. This study is designed to investigate the ability of udenafil, a newly developed long-acting PDE5 inhibitor, to improve functional capacity and hemodynamic status in a cohort of chronic systolic heart failure (SHF) patients.Methods/designStable, chronic SHF patients will be randomly assigned to placebo (26 patients) or udenafil at a dose of 50 mg twice per day (26 patients) for the first 4 weeks followed by 100 mg twice daily for the next 8 weeks. Eligibility criteria will be age ≥18 years, clinical diagnosis of chronic SHF with current New York Heart Association class II to IV symptoms, left ventricular ejection fraction ≤ 40%, and experience of at least one of following during the 12 months prior to study entry: hospitalization for decompensated heart failure, acute treatment with intravenous loop diuretics or hemofiltration, or pulmonary artery systolic pressure ≥40mmHg on transthoracic echocardiography. Pharmacological therapy for SHF will be optimized in all patients at least 30 days before study entry. The primary outcome will be the change of maximal oxygen uptake, assessed by cardiopulmonary exercise testing. Secondary outcomes will include changes in ventilatory efficiency (minute ventilation/carbon dioxide production slope), left ventricular systolic and diastolic parameters, pulmonary artery systolic pressure, plasma concentration of brain natriuretic peptide, occurrence of mortality or hospitalization for heart failure, and the occurrence of any adverse event.Clinical trial registrationUnique identifier: NCT01646515

show abstract

DA-8159, a New PDE5 Inhibitor, Attenuates the Development of Compensatory Right Ventricular Hypertrophy in a Rat Model of Pulmonary Hypertension

Cited by 15 publications

References 29 publications

Chronic treatment of DA-8159, a new phosphodiesterase type V inhibitor, attenuates endothelial dysfunction in stroke-prone spontaneously hypertensive rat

Chronic treatment of DA-8159, a new phosphodiesterase type V inhibitor, attenuates endothelial dysfunction in stroke-prone spontaneously hypertensive rat

Chronic administration of phosphodiesterase 5 inhibitor improves erectile and endothelial function in a rat model of diabetes

ULTIMATE-SHF trial (UdenafiL Therapy to Improve symptoMAtology, exercise Tolerance and hEmodynamics in patients with chronic systolic heart failure): study protocol for a randomized, placebo-controlled, double-blind trial

Contact Info

Product

Resources

About