Angiotensinogeen als nieuw aangrijppunt bij hypertensie: opkomst van RNA-medicijnen (zilebesiran, tonlamarsen)

Hypertension, Volume 83, Issue 6, Page e26091, June 1, 2026. Hypertension is the leading modifiable risk factor for cardiovascular disease, stroke, chronic kidney disease, and premature mortality. Although AGT (angiotensinogen) is a central component of the renin-angiotensin-aldosterone system, it was historically viewed primarily as a biochemical substrate rather than an active regulator of blood pressure and received less attention as a therapeutic target in hypertension compared with downstream renin-angiotensin-aldosterone system components such as angiotensin-converting enzyme and angiotensin II receptors. However, emerging evidence highlights its dynamic, tissue-specific role in blood pressure regulation and its responsiveness to metabolic, hormonal, and inflammatory stimuli. This narrative review examines the molecular biology, structure-function relationships, and regulatory mechanisms of AGT, including genetic variants such as M235T and −6G>A, which contribute to interindividual and population-level susceptibility to hypertension. We further explore AGT’s pathogenic role in salt-sensitive hypertension, obesity-related inflammation, and renin-angiotensin-aldosterone system escape phenomena. Recent translational advances, including RNA-based therapeutics such as small interfering RNAs (zilebesiran) and antisense oligonucleotides (tonlamarsen), demonstrate promising blood pressure reductions and favorable safety profiles in clinical trials. AGT also shows potential as a biomarker for hypertensive nephropathy and treatment responsiveness. This review underscores the value of AGT as an upstream therapeutic target and diagnostic marker, offering new avenues for precision medicine and long-acting strategies in the management of both conventional and resistant hypertension while possibly addressing medication adherence-related obstacles.