Acute hypertension-mediated end organ damage in malignant hypertension. In malignant hypertension, a sudden increase in vascular resistance and pressure-induced natriuresis trigger a vicious circle leading to renin–angiotensin system activation and a further increase in blood pressure and microcirculatory damage. Autoregulation failure and microcirculatory damage are at the foundation of the target organ damage associated with malignant hypertension. RAS, renin–angiotensin system.