A GENETIC MODEL OF MALIGNANT PHASE HYPERTENSION IN RATS

A genetic model of malignant phase hypertension in rats is described w hich closely parallels the natural history of untreated human malignan t phase hypertension. Although the factors initiating transition from essential hypertension to the accelerated phase in humans remain unkno wn, we report the characteristics of a genetically determined and repr oducible phenotype which was found to result from a cross between hype rtensive transgenic Ren-2 rats and normotensive Sprague-Dawley (Edinbu rgh) rats. Male F1 hybrids developed malignant phase hypertension with a penetrance of 73.5% (95% confidence limits 65.7 to 81.3%) by 100 da ys of age. Phenotypic features included an accelerated rise in blood p ressure, fibrinoid necrosis, activation of the renal renin-angiotensin system and microangiopathic hemolytic anemia. In an analytical cross no significant difference in blood pressure was observed between malig nant phase and non-malignant phase animals prior to transition, implyi ng that a factor in addition to hypertension appears necessary for ind ucing transition to the malignant phase phenotype. Segregation of the malignant phenotype suggested that susceptibility is determined by at most two genetic loci.