The Role of the Renin–Angiotensin–Aldosterone System in Hypertensive Emergencies

Background: Hypertensive emergencies are severe clinical conditions characterized by sudden elevation of blood pressure accompanied by acute target organ damage, including cardiovascular, cerebrovascular, renal, and retinal complications. Although blood pressure elevation is the defining feature, accumulating evidence indicates that activation of the renin–angiotensin–aldosterone system (RAAS) may play a central role in the molecular and cellular mechanisms underlying vascular injury. This review critically examines the current evidence regarding the involvement of the RAAS in the pathophysiology of hypertensive emergencies, highlighting its contribution to endothelial dysfunction, oxidative stress, inflammation, microvascular damage, and target organ injury, as well as its therapeutic implications and future research perspectives. Methods: A comprehensive narrative review of the literature was conducted using narrative reviews, systematic reviews, meta-analyses, experimental, translational, and clinical studies published in major biomedical databases, with particular emphasis on recent evidence addressing RAAS signaling, hypertensive emergencies, target organ damage, and emerging therapeutic approaches. Current international guidelines and landmark studies were also considered to provide an updated overview of the diseases. Results: Available evidence indicates that excessive activation of the classical ACE/angiotensin II/AT1 receptor axis contributes to acute vasoconstriction, endothelial dysfunction, reactive oxygen species generation, inflammatory activation, impaired vascular autoregulation, and microvascular injury, thereby promoting acute damage to the brain, heart, kidneys, retina, and large arteries. Conversely, the counter-regulatory ACE2/angiotensin-(1–7)/Mas receptor axis exerts protective vascular effects, although its role in hypertensive emergencies is unclear. Current therapies primarily focus on controlled blood pressure reduction, whereas the potential benefits of targeted RAAS modulation during the acute phase remain uncertain. Conclusions: The RAAS may play an important role in the pathophysiological processes underlying hypertensive emergencies, extending beyond its classical function of blood pressure regulation. However, direct human evidence remains limited and heterogeneous, warranting caution in interpreting these findings. A deeper understanding of the interactions between RAAS activation, vascular dysfunction, and target organ injury could help identify potential biomarkers and therapeutic targets, ultimately contributing to improved management and prognosis in patients with hypertensive emergencies.