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.