Phosphodiesterase type 5 inhibitors in the treatment of pulmonary arterial hypertension

Kılıçkesmez, Kadriye Orta; Küçükoğlu, Mehmet Serdar

doi:10.5152/akd.2010.125

Cited by 4 publications

(3 citation statements)

References 12 publications

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“…18,19 In addition, recent studies have shown that sildenafil has beneficial effects on fracture healing by enhancing bone formation in experimental animal models. [20][21][22] This effect may be related to the beneficial effects of PDE5 inhibitors on vasodilatation, 23,24 angiogenesis 25,26 and the NO/cGMP/PKG signalling pathway. 27 In previous studies, it has been shown that there is a positive correlation between reactive oxygen species (ROS) and osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

The effect of PDE5 inhibitors on bone and oxidative damage in ovariectomy-induced osteoporosis

Hakan

Huyut

Yıldırım

et al. 2017

Exp Biol Med (Maywood)

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The results in our study appear to establish the osteoporosis model and provide evidence of the positive effects of three separate PDE5 inhibitors (vardenafil, udenafil, and tadalafil). The positive effects of these PDE5 inhibitors are investigated and demonstrated by the bone mass density and bone resorption markers. These effects are associated with significant demonstrated antioxidant activities. Osteoporosis is a significant major public health problem especially in more aged populations. Advances in identifying and understanding new potential therapeutic modalities for this disease are significant. This study provides such an advance. AbstractOsteoporosis is a major public health problem associated with many factors, and it affects more than 50% of women over 50 years old. In the current study, our purpose was to investigate the effects of phosphodiestarase-5 inhibitors on osteoporosis via the nitric oxide/3 0 ,5 0 -cyclic guanosine monophosphate/protein kinase G signalling pathway. A total of 50 female albino Wistar rats were separated into five groups. The first group was appointed as the healthy control group with no ovariectomy. All animals in the other groups underwent a bilateral ovariectomy. Six months after the ovariectomy, vardenafil, udenafil and tadalafil were given to the third, fourth and fifth groups, respectively, but were not administered to the positive control group (10 mg/kg per day for two months). The bone mineral density values were determined using a densitometry apparatus for all groups pre-and post-ovariectomy as well as after treatment. The levels of nitric oxide, endothelial nitric oxidesynthase, asymmetric dimethylarginine, 3 0 ,5 0 -cyclic guanosine monophosphate, protein kinase G, phosphodiestarase-5, pyridinoline, deoxypyridinoline, carboxyterminal telopeptide fragments and plasma carboxy terminal propeptide of type I collagen were determined using an enzyme linked immunosorbent assay. The levels of malondialdehyde, 8-hydroxy-2-deoxy guanosine, deoxyguanosine and coenzyme Q10 were determined by a high-performance liquid chromatography assay. Additionally, the right femoral trabecular bone density and the epiphyseal plate were measured in all groups. Angiogenesis was histologically observed in the bone tissue. In addition, we determined that the inhibitors may have caused a positive impact on the increased bone mass density and reduction of bone resorption markers. We also observed the positive effects of these inhibitors on oxidative stress. In conclusion, these phosphodiestarase-5 inhibitors increase angiogenesis in bone tissue and improve the re-formation rate of bone in rats with osteoporosis.

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Section: Introductionmentioning

confidence: 99%

The effect of PDE5 inhibitors on bone and oxidative damage in ovariectomy-induced osteoporosis

Hakan

Huyut

Yıldırım

et al. 2017

Exp Biol Med (Maywood)

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“…Sildenafil, erektil disfonksiyon ve pulmoner hipertansiyon tedavisinde kullanılmaktadır 16 . Fosfodiesteraz inhibisyonu ile cAMP-cGMP yolunda düzenleyici etkisi, güçlü vazodilatatör ve hücre koruyucu özellikleri ile sitotoksisiteyi önlediği deneysel olarak gösterilmiştir.…”

Section: Discussionunclassified

•Effects of sildenafil on isoniazid and streptomycin neurotoxicity in rats

Açar¹

2011

Dicle Med J

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Objectives: Neurotoxicity due to isoniazide (INH) and streptomycin has been reported. Experimental studies reported that sildenafil can reduce toxic effects of some drugs. The aim of this study was to investigate the possible toxic effects of long-term streptomycin and INH use and probable protective effects of sildenafil on the rat brain and cerebellum. Materials and methods: In this study, 78 rats were divided into eight groups as follows; control group (n=10), INH group (n=10), streptomycin group (n=10), INH + streptomycin group (n=10), sildenafil group (n=10), INH+sildenafil group (n=10), streptomycin+sildenafil group (n=8) and INH+streptomycin + sildenafil group (n=10). At the end of 30 days of the treatment, the brain and cerebellar tissues of the rats were examined histopathologically. On the all tissues, inflammation, edema, congestion, degeneration and necrosis were investigated under a light microscope by the same pathologist blinded to the experimental groups. Results: Degeneration was significantly more prominent in the streptomycin group compared with the control group (respectively, p=0.002, p<0.001) on the cerebellum and cerebrum of the rats. INH+streptomycin group showed increased degenerative changes in the brain tissues compared with the INH group (p=0.006). Cerebellar degeneration on the INH+streptomycin+sildenafil group was the most obvious when compared to the control group (p=0.001) and degenerative changes was more obvious in the INH+streptomycin+sildenafil group when compared to the INH+streptomycin group (p=0.032). Conclusion: INH and streptomycin combination showed increased neurotoxicity in the rats. However, sildenafil worsened this neurotoxicity. Electron microscopic and immunohistochemical further studies are needed to investigate some aspects of this toxicity.

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“…2012; Levin and White, 2011; Maki et al . 2011; Kiliçkesmez and Küçükoğlu, 2010]. It has been advocated to start tadalafil coadministration in patients with 6MWD of less than 380 m, signs of right-sided heart failure, persistent functional class III or IV symptoms refractory to treatment with one medication, or those patients who did not respond to the first-line therapy [Chin and Rubin, 2008; Hoeper et al .…”

Section: Clinical Study Data Reviewmentioning

confidence: 99%

Tadalafil as monotherapy and in combination regimens for the treatment of pulmonary arterial hypertension

Udeoji

Schwarz

2012

Ther Adv Respir Dis

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The purpose of this review is to evaluate the use of tadalafil as monotherapy and in combination regimens for the treatment of pulmonary arterial hypertension (PAH). A systematic English language search of the medical literature using PubMed was conducted between January 1960 and May 2012 using the search terms 'tadalafil', 'therapy', 'pulmonary (arterial) hypertension' and 'combination therapy'. Special emphasis was given to controlled clinical trials and case studies relevant for the use of tadalafil in PAH. The search revealed 113 relevant publications, 31 of which were clinical trials, 52 were reviews and 12 were case reports. Of these, 12 were clinical studies in human patients with PAH who were treated with tadalafil alone, and seven were clinical studies in human patients with PAH who were treated with tadalafil in combination with other agents. Only clinical studies in human patients were included. Exclusion criteria were monotherapy other than using tadalafil and any combination therapy that excluded tadalafil as part of the treatment regimen. Overall, 1353 human subjects were studied; 896 were treated with tadalafil alone while 457 subjects were treated with tadalafil in coadministration. Tadalafil appears to be an effective and a safe treatment option for patients with PAH. It improves clinical status, exercise capacity, hemodynamic parameters, compliance issues and quality of life and reduces the occurrence of clinical worsening. Tadalafil in combination therapy seems to be additive and synergistic in relaxing pulmonary vascular muscle cells but more clinical trials on human subjects are warranted.

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Phosphodiesterase type 5 inhibitors in the treatment of pulmonary arterial hypertension

Cited by 4 publications

References 12 publications

The effect of PDE5 inhibitors on bone and oxidative damage in ovariectomy-induced osteoporosis

The effect of PDE5 inhibitors on bone and oxidative damage in ovariectomy-induced osteoporosis

•Effects of sildenafil on isoniazid and streptomycin neurotoxicity in rats

Tadalafil as monotherapy and in combination regimens for the treatment of pulmonary arterial hypertension

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