ArticleJournal of the American Heart Association2022
Conventional Vasopressor and Vasopressor-Sparing Strategies to Counteract the Blood Pressure-Lowering Effect of Small Interfering RNA Targeting Angiotensinogen.
Article in Journal of the American Heart Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Zilebesiran in Hypertension: Reversibility, Acute Illness, and Therapeutic Flexibility.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2026Review
- Zilebesiran, a Small Interfering RNA Therapeutic Targeting Angiotensinogen: Mechanism, Clinical Evidence, Safety, and Implementation Considerations.Life (Basel, Switzerland) · 2026Review
- High Salt Intake Enhances the REVERSIR-Induced Recovery of Blood Pressure After Angiotensinogen siRNA Treatment.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Long-acting RNAi therapeutics in hypertension: limitations of single-target AGT silencing and rational multi-target synergistic strategies.Frontiers in pharmacology · 2026Review
- Zilebesiran as an Innovative siRNA-Based Therapeutic Approach for Hypertension: Emerging Perspectives in Cardiovascular Medicine.International journal of molecular sciences · 2025Review
- Zilebesiran-Small Interfering RNAs as Prospective New Drug in the Treatment of Hypertension.Journal of clinical medicine · 2025Review
- Novel pharmacological approaches to lowering blood pressure and managing hypertension.Nature reviews. Cardiology · 2025Review
- Advancing hypertension management: the role of zilebesiran as an siRNA therapeutic agent.Annals of medicine and surgery (2012) · 2025Review
- Small Interfering RNA Therapy for the Management and Prevention of Hypertension.Current hypertension reports · 2025Review
- Emerging RNAi Therapies to Treat Hypertension.Molecular diagnosis & therapy · 2025Review
- Exploratory Studies on RNAi-Based Therapies Targeting Angiotensinogen in Hypertension: Scoping Review.Journal of personalized medicine · 2024Review
- Counteracting Angiotensinogen Small-Interfering RNA-Mediated Antihypertensive Effects With REVERSIR.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Angiotensinogen as a Therapeutic Target for Cardiovascular and Metabolic Diseases.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- A Comprehensive Retrospective Study on the Mechanisms of Cyclic Mechanical Stretch-Induced Vascular Smooth Muscle Cell Death Underlying Aortic Dissection and Potential Therapeutics for Preventing Acute Aortic Aneurysm and Associated Ruptures.International journal of molecular sciences · 2024Review
- RNA Interference as a Therapeutic Approach for Managing Hypertension.Clinical journal of the American Society of Nephrology : CJASN · 2024Article
- Molecular Therapies in Cardiovascular Diseases: Small Interfering RNA in Atherosclerosis, Heart Failure, and Hypertension.International journal of molecular sciences · 2023Review
- New Approaches Targeting the Renin-Angiotensin System: Inhibition of Brain Aminopeptidase A, ACE2 Ubiquitination, and Angiotensinogen.The Canadian journal of cardiology · 2023Review
- Functional Exploration of Conserved Sequences in the Distal Face of Angiotensinogen-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Blood pressure-independent renoprotective effects of small interference RNA targeting liver angiotensinogen in experimental diabetes.British journal of pharmacology · 2023Article
- Small Interfering RNA Therapeutics in Hypertension: A Viewpoint on Vasopressor and Vasopressor-Sparing Strategies for Counteracting Blood Pressure Lowering by Angiotensinogen-Targeting Small Interfering RNA.Journal of the American Heart Association · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
Background A single dose of small interfering RNA (siRNA) targeting liver angiotensinogen eliminates hepatic angiotensinogen and lowers blood pressure. Angiotensinogen elimination raises concerns for clinical application because an angiotensin rise is needed to maintain perfusion pressure during hypovolemia. Here, we investigated whether conventional vasopressors can raise arterial pressure after angiotensinogen depletion. Methods and Results Spontaneously hypertensive rats on a low-salt diet were treated with siRNA (10 mg/kg fortnightly) for 4 weeks, supplemented during the final 2 weeks with fludrocortisone (6 mg/kg per day), the α-adrenergic agonist midodrine (4 mg/kg per day), or a high-salt diet (all groups n=6-7). Pressor responsiveness to angiotensin II and norepinephrine was assessed before and after siRNA administration. Blood pressure was measured via radiotelemetry. Depletion of liver angiotensinogen by siRNA lowered plasma angiotensinogen concentrations by 99.2±0.1% and mean arterial pressure by 19 mm Hg. siRNA-mediated blood pressure lowering was rapidly reversed by intravenous angiotensin II or norepinephrine, or gradually reversed by fludrocortisone or high salt intake. Midodrine had no effect. Unexpectedly, fludrocortisone partially restored plasma angiotensinogen concentrations in siRNA-treated rats, and nearly abolished plasma renin concentrations. To investigate whether this angiotensinogen originated from nonhepatic sources, fludrocortisone was administered to mice lacking hepatic angiotensinogen. Fludrocortisone did not increase angiotensinogen in these mice, implying that the rise in angiotensinogen in the siRNA-treated rats must have depended on the liver, most likely reflecting diminished cleavage by renin. Conclusions Intact pressor responsiveness to conventional vasopressors provides pharmacological means to regulate the blood pressure-lowering effect of angiotensinogen siRNA and may support future therapeutic implementation of siRNA.
Indexed as
Identifiers
What OpenQuestion holds
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.