Malignant Hypertension - the Role of the Paracrine Renin-angiotensin System

Malignant hypertension remains one of the life-threatening complications of blood pressure elevation. It is a clinico-pathological syndrome of severe blood pressure elevation combined with malignant vascular injury. This is a characteristic form of vascular damage, with two elements: fibrinoid necrosis and endarteritis proliferans. Although the morphology of these has been well described, the molecular events are not fully understood. This review summarizes the evidence from transgenic animals for a role for the activation of a local paracrine renin-angiotensin system in the pathogenesis of malignant vascular injury. These animal models provide pathological, pharmacological, and genetic evidence supporting the hypothesis that intra-renal generation of angiotensin 2 and exposure of the microcirculation to elevated blood pressure co-operate in causing tissue damage in malignant hypertension.