Usefulness of Intravenous Adenosine in Idiopathic Pulmonary Arterial Hypertension as a Screening Agent for Identifying Long-Term Responders to Calcium Channel Blockers

Zuo, Xianbo; Rui, Zhang; Jiang, Xin; Li, Xinli; Feng, Zhang; Xie, Wei; Wang, Hong; Jing, Zhi‐Cheng

doi:10.1016/j.amjcard.2012.02.026

Cited by 16 publications

(10 citation statements)

References 20 publications

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“…Acute vasoreactivity testing is most commonly performed using intravenous epoprostenol, 43 , 44 intravenous adenosine, 45 or inhaled nitric oxide. 44 Acute testing using intravenous epoprostenol was shown to be useful for identifying patients with good prognosis; however, a good response to epoprostenol does not indicate that all patients will have a long-term response to CCBs.…”

Section: Acute Vasoreactivity Testingmentioning

confidence: 99%

Epoprostenol sodium for treatment of pulmonary arterial hypertension

Saito¹,

Nakamura²,

Akagi³

et al. 2015

VHRM

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The release of endogenous prostacyclin (PGI2) is depressed in patients with pulmonary arterial hypertension (PAH). PGI2 replacement therapy by epoprostenol infusion is one of the best treatments available for PAH. Here, we provide an overview of the current clinical data for epoprostenol. Epoprostenol treatment improves symptoms, exercise capacity, and hemodynamics, and is the only treatment that has been shown to reduce mortality in patients with idiopathic PAH (IPAH) in randomized clinical trials. We have reported that high-dose epoprostenol therapy (>40 ng/kg/min) also results in marked hemodynamic improvement in some patients with IPAH. High-dose epoprostenol has a pro-apoptotic effect on PAH-PASMCs via the IP receptor and upregulation of Fas ligand (FasL) in vitro. However, long-term intravenous administration of epoprostenol is sometimes associated with catheter-related infections and leads to considerable inconvenience for the patient. In the future, the development of new routes of administration or the development of powerful PGI2 analogs, IP-receptor agonists, and gene and cell-based therapy enhancing PGI2 production with new routes of administration is required.

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Section: Acute Vasoreactivity Testingmentioning

confidence: 99%

Epoprostenol sodium for treatment of pulmonary arterial hypertension

Saito¹,

Nakamura²,

Akagi³

et al. 2015

VHRM

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“…[21][22][23] Pharmacological study demonstrated that patients with PAH intravenous infusion of adenosine at an appropriate dose could effectively decrease mPAP and PVR. 24 These findings implied that genetic inactivation of adenosine A 2A R caused PAH. Moreover, mutations in BMPR-II and impaired responses to BMP-specific SMADs are acknowledged as critical in the development of PAH, which is associated with pulmonary artery endothelial cell apoptosis and the loss of small vessels.…”

Section: Discussionmentioning

confidence: 97%

Absence of the Adenosine A2A Receptor Confers Pulmonary Arterial Hypertension Through RhoA/ROCK Signaling Pathway in Mice

Shang¹,

Chen

et al. 2015

Journal of Cardiovascular Pharmacology

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Numerous evidence suggests that RhoA/Rho kinase (ROCK) signaling pathway plays an important role in the pathogenesis of pulmonary arterial hypertension (PAH), but little is known about its effects on the development of PAH in mice with absence of the adenosine A2A receptor (A2AR). Eight A2AR knockout (KO) and 8 wild-type mice were used. Morphometric analysis of pulmonary arterioles included right ventricle/left ventricle plus ventricular septum (Fulton index), vessel wall thickness/total vascular diameter (WT%), and vessel wall area/total vascular area (WA%). The expression of RhoA and ROCK1 mRNA was determined by real-time polymerase chain reaction. The expression of RhoA, ROCK1, and phosphorylation of myosin phosphatase target subunit 1 proteins in pulmonary tissue was tested by Western blot. The position of ROCK1 protein was evaluated by immunohistochemistry. Compared with wild-type mice, A2AR KO mice displayed (1) increased Fulton index, WT%, and WA% (P < 0.01); (2) increased mRNA expression of RhoA and ROCK1 (each P < 0.05); (3) increased protein expression of RhoA, ROCK1, and phosphorylation of myosin phosphatase target subunit 1 (each P < 0.01); (4) increased location of ROCK1 protein in endothelial and smooth muscle cells of pulmonary artery, bronchial, and alveolar epithelial cells. Activation of RhoA/ROCK signaling pathway may cause pulmonary vascular constriction, pulmonary artery remodeling, and PAH in adenosine A2A receptor KO mice.

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“…Therapeutic efficacy has also been seen in patients with PH associated with congenital heart disease [73] and prematurity in the neonate [74,75]. Nevertheless, only around 10-20% of patients with idiopathic PAH had a reduction in their PAP with adenosine infusion [76,77]. The utility of adenosine as a therapeutic strategy has been hampered by its exceptionally short half-life (5-10 s), and its propensity for systemic effects including hypotension with accompanying increased heart rate and cardiac output.…”

Section: Purinergic Signalling Is Disrupted In Pahmentioning

confidence: 99%

CD39 in the development and progression of pulmonary arterial hypertension

Willcox

Lee

Nandurkar

et al. 2022

Purinergic Signalling

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Pulmonary arterial hypertension (PAH) is a devastating progressive disease characterised by pulmonary arterial vasoconstriction and vascular remodelling. Endothelial dysfunction has emerged as a contributing factor in the development of PAH. However, despite progress in the understanding of the pathophysiology of this disease, current therapies fail to impact upon long-term outcomes which remain poor in most patients. Recent observations have suggested the disturbances in the balance between ATP and adenosine may be integral to the vascular remodelling seen in PAH. CD39 is an enzyme important in regulating these nucleos(t)ides which may also provide a novel pathway to target for future therapies. This review summarises the role of adenosine signalling in the development and progression of PAH and highlights the therapeutic potential of CD39 for treatment of PAH.

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Usefulness of Intravenous Adenosine in Idiopathic Pulmonary Arterial Hypertension as a Screening Agent for Identifying Long-Term Responders to Calcium Channel Blockers

Cited by 16 publications

References 20 publications

Epoprostenol sodium for treatment of pulmonary arterial hypertension

Epoprostenol sodium for treatment of pulmonary arterial hypertension

Absence of the Adenosine A2A Receptor Confers Pulmonary Arterial Hypertension Through RhoA/ROCK Signaling Pathway in Mice

CD39 in the development and progression of pulmonary arterial hypertension

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