Genetic predisposition to stroke in spontaneously hypertensive rats

Hypertension and stroke in spontaneously hypertensive rats (SHR) were investigated genetically using stroke-prone SHR (A3), stroke-resistant SHR (C) and their hybrids, hybrid of A3 and C (F1), offspring of F1 X F1 (F2), and those of backcrossing of F1 to the respective parental strains, BC(F1 X A3) and BC(F1 X C). The average blood pressure measured without anesthesia increased in the following order during the experimental period: C less than BC (F1 X C) less than F1 approximately F2 less than BC(F1 X A3) less than A3. The F2 represented a wider spread of variation than the F1, with some of the pressure extending into the range of both parental strains. When the drinking water was replaced with a 1% salt solution, the blood pressure increased and the onset of stroke markedly accelerated in all groups of SHR. Under the hypertensive conditions, the incidence of stroke was associated with A3-gene concentration rather than with the level of blood pressure. Similar but less dramatic effects of salt were observed in another series of hybrid groups derived from A3 and normal Wistar-Kyoto rats. These findings suggest that the genetic factors are of great importance in the development of stroke as well as hypertension in the SHR.