Sildenafil for Pulmonary Arterial Hypertension

Bhogal, Sukhdeep; Khraisha, Ola; Madani, Mohammad Al; Treece, Jennifer; Baumrucker, Steven J.; Paul, Timir K.

doi:10.1097/mjt.0000000000000766

Cited by 46 publications

(29 citation statements)

References 29 publications

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“…It is pointed out that the combination of drugs can improve the symptoms and delay the progress of PH, but the effect is still not as expected or cured. 195–197 We need to find some new therapeutic targets in different directions. In our description of ions and their channels, the above-mentioned ions and their channels can be used as research targets for the treatment of PH.…”

Section: Discussionmentioning

confidence: 99%

The mechanism of ions in pulmonary hypertension

Liu

fu²,

Tian

et al. 2021

Pulm. circ.

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Pulmonary hypertension（PH）is a kind of hemodynamic and pathophysiological state, in which the pulmonary artery pressure (PAP) rises above a certain threshold. The main pathological manifestation is pulmonary vasoconstriction and remodelling progressively. More and more studies have found that ions play a major role in the pathogenesis of PH. Many vasoactive substances, inflammatory mediators, transcription-inducing factors, apoptosis mediators, redox substances and translation modifiers can control the concentration of ions inside and outside the cell by regulating the activity of ion channels, which can regulate vascular contraction, cell proliferation, migration, apoptosis, inflammation and other functions. We all know that there are no effective drugs to treat PH. Ions are involved in the occurrence and development of PH, so it is necessary to clarify the mechanism of ions in PH as a therapeutic target for PH. The main ions involved in PH are calcium ion (Ca2+), potassium ion (K+), sodium ion (Na+) and chloride ion (Cl–). Here, we mainly discuss the distribution of these ions and their channels in pulmonary arteries and their role in the pathogenesis of PH.

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Section: Discussionmentioning

confidence: 99%

The mechanism of ions in pulmonary hypertension

Liu

fu²,

Tian

et al. 2021

Pulm. circ.

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“…8 For example, sildenafil was demonstrated to inhibit pulmonary vascular remodeling and approved for treatment of PAH by the Food and Drug Administration (FDA) in 2005, but there are many adverse reactions and side effects. [9][10][11] MAPK cascade activation plays center roles in many signal pathways, it receives membrane receptor exchanged and transferred signal and then sends into cell nucleus, and it shows key roles in many cell proliferation-related signals. 12,13 MAPK stays in stable condition regularly; however, when cells are activated by growth factors or other reasons, MAPK could receive the MKK and MKKK activating signal and become phosphorylated successively.…”

Section: Introductionmentioning

confidence: 99%

Baicalin prevents pulmonary arterial remodeling in vivo via the AKT/ERK/NF‐κB signaling pathways

et al. 2019

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Pulmonary arterial hypertension is a rapidly progressive and often fatal disease. As the pathogenesis of pulmonary arterial hypertension remains unclear, there is currently no good drug for pulmonary arterial hypertension and new therapy is desperately needed. This study investigated the effects and mechanism of baicalin on vascular remodeling in rats with pulmonary arterial hypertension. A rat pulmonary arterial hypertension model was constructed using intraperitoneal injection of monocrotaline, and different doses of baicalin were used to treat these rats. The mean pulmonary arterial pressure (mPAP) and right ventricular systolic pressure (RVSP) were measured with a right heart catheter. Moreover, the hearts were dissected to determine the right ventricular hypertrophy index (RVHI). The lung tissues were stained with H&E and Masson's staining to estimate the pulmonary vascular remodeling and collagen fibrosis, and the expression of proteins in the AKT, ERK, and NF-κB p65 phosphorylation (p-AKT, p-ERK, p-p65) was examined by Western blot analysis. We found that compared with untreated pulmonary arterial hypertension rats, baicalin ameliorated pulmonary vascular remodeling and cardiorespiratory injury, inhibited p-p65 and p-ERK expression, and promoted p-AKT and p-eNOS expression. In conclusion, baicalin interfered with pulmonary vascular remodeling and pulmonary arterial hypertension development in rats through the AKT/eNOS, ERK and NF-κB signaling pathways.

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“…Similarly to PDE3 inhibitors, PDE5 inhibitors, particularly dipyridamole, sildenafil, and tadalafil, have been used in the treatment of PPHN [164,181,182] and pulmonary hypertension of different origin including hypoxemic pulmonary hypertension [183][184][185][186]. In patients with ARDS-associated pulmonary hypertension, sildenafil decreased mean pulmonary arterial pressure and pulmonary artery occlusion pressure, but decreased systemic mean arterial pressure and increased the shunt fraction [187].…”

Section: Selective Pde Inhibitors In Patients With Ardsmentioning

confidence: 99%

Phosphodiesterase Inhibitors in Acute Lung Injury: What Are the Perspectives?

Mokrá

Mokrý

2021

IJMS

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Despite progress in understanding the pathophysiology of acute lung damage, currently approved treatment possibilities are limited to lung-protective ventilation, prone positioning, and supportive interventions. Various pharmacological approaches have also been tested, with neuromuscular blockers and corticosteroids considered as the most promising. However, inhibitors of phosphodiesterases (PDEs) also exert a broad spectrum of favorable effects potentially beneficial in acute lung damage. This article reviews pharmacological action and therapeutical potential of nonselective and selective PDE inhibitors and summarizes the results from available studies focused on the use of PDE inhibitors in animal models and clinical studies, including their adverse effects. The data suggest that xanthines as representatives of nonselective PDE inhibitors may reduce acute lung damage, and decrease mortality and length of hospital stay. Various (selective) PDE3, PDE4, and PDE5 inhibitors have also demonstrated stabilization of the pulmonary epithelial–endothelial barrier and reduction the sepsis- and inflammation-increased microvascular permeability, and suppression of the production of inflammatory mediators, which finally resulted in improved oxygenation and ventilatory parameters. However, the current lack of sufficient clinical evidence limits their recommendation for a broader use. A separate chapter focuses on involvement of cyclic adenosine monophosphate (cAMP) and PDE-related changes in its metabolism in association with coronavirus disease 2019 (COVID-19). The chapter illuminates perspectives of the use of PDE inhibitors as an add-on treatment based on actual experimental and clinical trials with preliminary data suggesting their potential benefit.

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Sildenafil for Pulmonary Arterial Hypertension

Cited by 46 publications

References 29 publications

The mechanism of ions in pulmonary hypertension

The mechanism of ions in pulmonary hypertension

Baicalin prevents pulmonary arterial remodeling in vivo via the AKT/ERK/NF‐κB signaling pathways

Phosphodiesterase Inhibitors in Acute Lung Injury: What Are the Perspectives?

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