ArticleHypertension (Dallas, Tex. : 1979)2016
Urinary Proteolytic Activation of Renal Epithelial Na+ Channels in Chronic Heart Failure.
Article in Hypertension (Dallas, Tex. : 1979), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Cardiorenal Associations in Preclinical Modeling: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2026Pooled it
- Interaction Between the Sodium-Glucose-Linked Transporter 2 Inhibitor Dapagliflozin and the Loop Diuretic Bumetanide in Normal Human Subjects.Journal of the American Heart Association · 2018Trial
- Importance of early use of tolvaptan in hyponatremic acutely decompensated heart failure patients, a retrospective study.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2025Article
- The utility of urine sodium-guided diuresis during acute decompensated heart failure.Heart failure reviews · 2024Review
- Activation of renal epithelial NaFrontiers in pediatrics · 2024Article
- Oral Furosemide and Hydrochlorothiazide/Amiloride versus Intravenous Furosemide for the Treatment of Resistant Nephrotic Syndrome.Journal of clinical medicine · 2023Article
- A Serine Protease Inhibitor, Camostat Mesilate, Suppresses Urinary Plasmin Activity and Alleviates Hypertension and Podocyte Injury in Dahl Salt-Sensitive Rats.International journal of molecular sciences · 2023Article
- ENaC activation by proteases.Acta physiologica (Oxford, England) · 2022Review
- Renal denervation: basic and clinical evidence.Hypertension research : official journal of the Japanese Society of Hypertension · 2022Review
- Aldosterone-stimulated endothelial epithelial sodium channel (EnNaC) plays a role in cold exposure-induced hypertension in rats.Frontiers in pharmacology · 2022Article
- Biomarkers of Volume Overload and Edema in Heart Failure With Reduced Ejection Fraction.Frontiers in cardiovascular medicine · 2022Review
- Article
- Research Progress on the Cardiac Injury from ACE2 Targeting in SARS-CoV-2 Infection.Biomolecules · 2021Review
- Pathophysiology of Diuretic Resistance and Its Implications for the Management of Chronic Heart Failure.Hypertension (Dallas, Tex. : 1979) · 2020Review
- Elevated Plasmin(ogen) as a Common Risk Factor for COVID-19 Susceptibility.Physiological reviews · 2020Review
- SARS-CoV-2 receptor ACE2-dependent implications on the cardiovascular system: From basic science to clinical implications.Journal of molecular and cellular cardiology · 2020Review
- The "Three Italy" of the COVID-19 epidemic and the possible involvement of SARS-CoV-2 in triggering complications other than pneumonia.Journal of neurovirology · 2020Review
- Renal denervation improves sodium excretion in rats with chronic heart failure: effects on expression of renal ENaC and AQP2.American journal of physiology. Heart and circulatory physiology · 2019Article
- The Absence of the ACE N-Domain Decreases Renal Inflammation and Facilitates Sodium Excretion during Diabetic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2018Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
One of the key mechanisms involved in renal Na(+) retention in chronic heart failure (CHF) is activation of epithelial Na(+) channels (ENaC) in collecting tubules. Proteolytic cleavage has an important role in activating ENaC. We hypothesized that enhanced levels of proteases in renal tubular fluid activate ENaC, resulting in renal Na(+) retention in rats with CHF. CHF was produced by left coronary artery ligation in rats. By immunoblotting, we found that several urinary serine proteases were significantly increased in CHF rats compared with sham rats (fold increases: furin 6.7, prostasin 23.6, plasminogen 2.06, and plasmin 3.57 versus sham). Similar increases were observed in urinary samples from patients with CHF. Whole-cell patch clamp was conducted in cultured renal collecting duct M-1 cells to record Na(+) currents. Protease-rich urine (from rats and patients with CHF) significantly increased the Na(+) inward current in M-1 cells. Two weeks of protease inhibitor treatment significantly abrogated the enhanced diuretic and natriuretic responses to ENaC inhibitor benzamil in rats with CHF. Increased podocyte lesions were observed in the kidneys of rats with CHF by transmission electron microscopy. Consistent with these results, podocyte damage markers desmin and podocin expressions were also increased in rats with CHF (increased ≈2-folds). These findings suggest that podocyte damage may lead to increased proteases in the tubular fluid, which in turn contributes to the enhanced renal ENaC activity, providing a novel mechanistic insight for Na(+) retention commonly observed in CHF.
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Registered trials
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