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.
Fleming
S
S
Department of Pathology, University of Edinburgh Medical School, Edinburgh, UK. Stewart.Fleming@ed.ac.uk
D000804:Angiotensin II / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006974:Hypertension, Malignant / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012083:Renin