ArticleKidney international2015
Optimum AT1 receptor-neprilysin inhibition has superior cardioprotective effects compared with AT1 receptor blockade alone in hypertensive rats.
Article in Kidney international, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- Fulacimstat Reduces Angiotensin II in Kidney Allografts in a Cross-Sectional Exploratory Study.Kidney international reports · 2026Article
- Advances in the structural basis for angiotensin-1 converting enzyme (ACE) inhibitors.Bioscience reports · 2024Review
- Potential renoprotective effects and possible underlying mechanisms of angiotensin receptor-neprilysin inhibitors in cardiorenal syndrome.Frontiers in medicine · 2024Review
- Restoration of the gut barrier integrity and restructuring of the gut microbiome in aging by angiotensin-(1-7).Clinical science (London, England : 1979) · 2023Article
- Blood pressure-independent renoprotective effects of small interference RNA targeting liver angiotensinogen in experimental diabetes.British journal of pharmacology · 2023Article
- Kidney Angiotensin in Cardiovascular Disease: Formation and Drug Targeting.Pharmacological reviews · 2022Review
- SGLT2 inhibition effect on salt-induced hypertension, RAAS, and NaAmerican journal of physiology. Renal physiology · 2022Article
- Angiotensin Receptor-Neprilysin Inhibitor (ARNI) and Cardiac Arrhythmias.International journal of molecular sciences · 2021Review
- Therapeutic Assessment of Combination Therapy with a Neprilysin Inhibitor and Angiotensin Type 1 Receptor Antagonist on Angiotensin II-Induced Atherosclerosis, Abdominal Aortic Aneurysms, and Hypertension.The Journal of pharmacology and experimental therapeutics · 2021Article
- Dual Angiotensin Receptor and Neprilysin Inhibitor Ameliorates Portal Hypertension in Portal Hypertensive Rats.Pharmaceutics · 2020Article
- Novel Therapeutic Approaches Targeting the Renin-Angiotensin System and Associated Peptides in Hypertension and Heart Failure.Pharmacological reviews · 2019Review
- Intrarenal Renin-Angiotensin-System Dysregulation after Kidney Transplantation.Scientific reports · 2019Article
- Molecular regulation of the renin-angiotensin system by sodium-glucose cotransporter 2 inhibition in type 1 diabetes mellitus.Diabetologia · 2019Article
- ARNi: A Novel Approach to Counteract Cardiovascular Diseases.International journal of molecular sciences · 2019Review
- Chronic Kidney Disease as a Risk Factor for Heart Failure With Preserved Ejection Fraction: A Focus on Microcirculatory Factors and Therapeutic Targets.Frontiers in physiology · 2019Review
- Mycophenolate Mofetil Attenuates DOCA-Salt Hypertension: Effects on Vascular Tone.Frontiers in physiology · 2018Article
- Angiotensin II Receptor-Neprilysin Inhibitor Sacubitril/Valsartan Improves Endothelial Dysfunction in Spontaneously Hypertensive Rats.Journal of the American Heart Association · 2017Article
- Long-term neprilysin inhibition - implications for ARNIs.Nature reviews. Cardiology · 2017Review
- Beneficial Effects of Combined AT1 Receptor/Neprilysin Inhibition (ARNI) Versus AT1 Receptor Blockade Alone in the Diabetic Eye.Investigative ophthalmology & visual science · 2016Article
- From ARB to ARNI in Cardiovascular Control.Current hypertension reports · 2016Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neprilysin inhibitors prevent the breakdown of bradykinin and natriuretic peptides, promoting vasodilation and natriuresis. However, they also increase angiotensin II and endothelin-1. Here we studied the effects of a low and a high dose of the neprilysin inhibitor thiorphan on top of AT1 receptor blockade with irbesartan versus vehicle in TGR(mREN2)27 rats with high renin hypertension. Mean arterial blood pressure was unaffected by vehicle or thiorphan alone. Irbesartan lowered blood pressure, but after 7 days pressure started to increase again. Low- but not high-dose thiorphan prevented this rise. Only during exposure to low-dose thiorphan plus irbesartan did heart weight/body weight ratio, cardiac atrial natriuretic peptide expression, and myocyte size decrease significantly. Circulating endothelin-1 was not affected by low-dose thiorphan with or without irbesartan, but increased after treatment with high-dose thiorphan plus irbesartan. This endothelin-1 rise was accompanied by an increase in renal sodium-hydrogen exchanger 3 protein abundance, and an upregulation of constrictor vascular endothelin type B receptors. Consequently, the endothelin type B receptor antagonist BQ788 no longer enhanced endothelin-1-induced vasoconstriction (indicative of endothelin type B receptor-mediated vasodilation), but prevented it. Thus, optimal neprilysin inhibitor dosing reveals additional cardioprotective effects on top of AT1 receptor blockade in renin-dependent hypertension.
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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.