The Renin—Angiotensin System and the Pathogenesis of Vascular Disease in Malignant Hypertension

1. The syndrome of malignant hypertension in man and animals has three fundamental components: high blood pressure, activation of the renin—angiotensin system and the rapid development of necrotizing arteriolar disease. 2. The high blood pressure can be associated with different conformations of the arteriolar microcirculation. The emergence of an arteriolar reaction pattern characterized by the formation of focal dilatations, with intervening constricted segments, is of fundamental pathophysiological importance. 3. Activation of the renin system is reflected in an increased renin secretion rate from the kidneys and an increased rate of angiotensin II generation in the pulmonary vascular bed. 4. The crucial pathogenetic process, leading eventually to severe arteriolar wall damage, is a penetration of plasmatic macromolecules into the wall of distended arteriolar segments, as observed in states of severe experimental hypertension. 5. Renin can induce vascular disease, but hypersecretion of renin is not a necessary condition for the development of hypertensive arteriolar necrosis.