ArticleHypertension (Dallas, Tex. : 1979)2024
Counteracting Angiotensinogen Small-Interfering RNA-Mediated Antihypertensive Effects With REVERSIR.
Article in Hypertension (Dallas, Tex. : 1979), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Breakthrough drugs in the treatment of hypertension-related disease.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Review
- Zilebesiran in Hypertension: Reversibility, Acute Illness, and Therapeutic Flexibility.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2026Review
- Pendrin inhibitor PDSinh-C01 reverses salt-sensitive hypertension and metabolic acidosis in the 5/6 nephrectomy rat model.Pflugers Archiv : European journal of physiology · 2026Article
- 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
- A New Avenue for the Long-Term Upstream Inhibition of the Renin-Angiotensin-Aldosterone System by Inhibiting Angiotensinogen RNA.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2026Review
- 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
- Small Interfering RNA Therapy for the Management and Prevention of Hypertension.Current hypertension reports · 2025Review
- Arterial hypertension-clinical trials update 2024.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- RNA interference therapy in cardiology: will new targets improve therapeutic goals?Drugs in context · 2024Review
- Review
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9 authors.
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Abstract
backgroundSmall-interfering RNA (siRNA) targeting hepatic AGT (angiotensinogen) mRNA depletes AGT, lowering blood pressure for up to 6 months. However, certain situations may require a rapid angiotensin increase. The REVERSIR (RVR) - reverse siRNA silencing technology a potential approach to counteract siRNA effects.
methodsSpontaneously hypertensive rats received 10 mg/kg AGT siRNA, and 3 weeks later were given AGT-RVR (1, 10, or 20 mg/kg). One week after AGT-RVR dosing, a redose of AGT siRNA assessed its post-AGT-RVR effectiveness for 2 weeks. Additionally, the impact of AGT-RVR after an equihypotensive dose of valsartan (4 mg/kg per day) was examined.
resultsBaseline mean arterial pressure (MAP) was 144±1 mm Hg. AGT siRNA reduced MAP by ≈16 mm Hg and AGT by >95%, while renin increased 25-fold. All AGT-RVR doses restored MAP to baseline within 4 to 7 days. Notably, 10 and 20 mg/kg restored AGT and renin to baseline, while 1 mg/kg allowed ≈50% AGT restoration, with renin remaining above baseline. A second AGT siRNA treatment, following 1 mg/kg AGT-RVR, reduced MAP to the same degree as the initial dose, while following 10 mg/kg AGT-RVR, it resulted in ≈50% of the first dose's MAP effect at 2 weeks. The valsartan-induced MAP reduction was unaffected by AGT-RVR.
conclusionsIn spontaneously hypertensive rats, angiotensinogen-RVR dose-dependently reversed AGT siRNA-induced AGT reduction, normalizing MAP. MAP normalization persisted even with 50% recovered AGT levels, likely due to upregulated renin maintaining adequate angiotensin generation. Post-AGT-RVR dosing, a second AGT siRNA dose lowered MAP again.
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