ArticleHypertension (Dallas, Tex. : 1979)2012
Sildenafil prevents and reverses transverse-tubule remodeling and Ca(2+) handling dysfunction in right ventricle failure induced by pulmonary artery hypertension.
Article in Hypertension (Dallas, Tex. : 1979), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 111 citations in OpenAlex.
- Trial
- Beneficial effects of magnesium nitrate on disease severity in male rats with monocrotaline-induced pulmonary hypertension.Physiological reports · 2025Article
- Restoring Atrial T-Tubules Augments Systolic Ca Upon Recovery From Heart Failure.Circulation research · 2024Article
- Sex-dependent remodeling of right ventricular function in a rat model of pulmonary arterial hypertension.American journal of physiology. Heart and circulatory physiology · 2024Article
- Pulmonary Hypertension and Right Ventricle: A Pathophysiological Insight.Clinical Medicine Insights. Cardiology · 2024Review
- Correlative super-resolution analysis of cardiac calcium sparks and their molecular origins in health and disease.Open biology · 2023Article
- Three-dimensional visualization of the cardiac ryanodine receptor clusters and the molecular-scale fraying of dyads.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Article
- The SOCE Machinery: An Unbalanced Knowledge between Left and Right Ventricular Pathophysiology.Cells · 2022Review
- Dapagliflozin reduces the vulnerability of rats with pulmonary arterial hypertension-induced right heart failure to ventricular arrhythmia by restoring calcium handling.Cardiovascular diabetology · 2022Article
- The role of junctophilin proteins in cellular function.Physiological reviews · 2022Review
- Cross-bridge thermodynamics in pulmonary arterial hypertensive right-ventricular failure.Journal of applied physiology (Bethesda, Md. : 1985) · 2022Article
- Loss of cardiac myosin light chain kinase contributes to contractile dysfunction in right ventricular pressure overload.Physiological reports · 2022Article
- Inflammatory Glycoprotein 130 Signaling Links Changes in Microtubules and Junctophilin-2 to Altered Mitochondrial Metabolism and Right Ventricular Contractility.Circulation. Heart failure · 2022Article
- Calpain-2 specifically cleaves Junctophilin-2 at the same site as Calpain-1 but with less efficacy.The Biochemical journal · 2021Article
- Nanoscale Study of Calcium Handling Remodeling in Right Ventricular Cardiomyocytes Following Pulmonary Hypertension.Hypertension (Dallas, Tex. : 1979) · 2021Article
- The Physiology and Pathophysiology of T-Tubules in the Heart.Frontiers in physiology · 2021Review
- Targeting JP2: A New Treatment for Pulmonary Hypertension.Oxidative medicine and cellular longevity · 2021Review
- Treatment Targets for Right Ventricular Dysfunction in Pulmonary Arterial Hypertension.JACC. Basic to translational science · 2020Review
- Resveratrol Prevents Right Ventricle Remodeling and Dysfunction in Monocrotaline-Induced Pulmonary Arterial Hypertension with a Limited Improvement in the Lung Vasculature.Oxidative medicine and cellular longevity · 2020Article
- Nexilin Is a New Component of Junctional Membrane Complexes Required for Cardiac T-Tubule Formation.Circulation · 2019Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Right ventricular (RV) failure (RVF) is the main cause of death in patients with pulmonary artery hypertension (PAH). Sildenafil, a phosphodiesterase type 5 inhibitor, was approved recently for treatment of PAH patients. However, the mechanisms underlying RV contractile malfunction and the benefits of sildenafil on RV function are not well understood. We aimed to investigate the following: (1) the ultrastructural and excitation-contraction coupling alterations underlying PAH-induced RVF; (2) whether the ultrastructural changes are reversible; and (3) the mechanisms underlying the therapeutic benefits of sildenafil in PAH-RVF. We used a single injection of monocrotaline in Wistar rats to induce pulmonary vascular proliferation, which led to PAH and RVF. RV myocytes displayed severe transverse (T)-tubule loss and disorganization, as well as blunted and dys-synchronous sarcoplasmic reticulum Ca(2+) release. Sildenafil prevented and reversed the monocrotaline-induced PAH and LV filling impairment. Early intervention with sildenafil prevented RV hypertrophy and the development of RVF, T-tubule remodeling, and Ca(2+) handling dysfunction. Although late treatment with sildenafil did not reverse RV hypertrophy in animals with established RVF, RV systolic function was improved. Furthermore, late intervention partially reversed both the impairment of myocyte T-tubule integrity and Ca(2+) handling protein and sarcoplasmic reticulum Ca(2+) release function in monocrotaline-treated rats. In conclusion, PAH-induced increase in RV afterload causes severe T-tubule remodeling and Ca(2+) handling dysfunction in RV myocytes, leading to RV contractile failure. Sildenafil prevents and partially reverses ultrastructural, molecular, and functional remodeling of failing RV myocytes. Reversal of pathological T-tubule remodeling, although incomplete, is achievable without the regression of RV hypertrophy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.