CEREBRAL INFARCTION PRONENESS IN HYPERTENSION
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Sudden occlusion of the middle cerebral artery (MCA) in the 5 week old spontaneously hypertensive stroke prone rat (SHRSP) invariably results in a large cerebral ischemic infarct (1). In striking contrast, the aged matched genetically normotensive Wistar Kyoto rat (WKY) is protected from the lesion by a collateral circulation. Whether or not the proneness for cerebral infarction and altered collaterals in the SHRSP 1) are merely coincidental to the mechanism of hypertension, or 2) related to it through a common genetic etiology will be investigated. A comparison of SHRSP to any normotensive inbred strain cannot resolve the issue of independent genetic etiologies because the strains are presumably fixed for allelic differences at a large number of loci unrelated to blood pressure regulation. The possible etiological involvement of a trait can be established by showing that it cosegregates with an increment of BP, while all unrelated traits are expected to segregate at random in BC and F2 progrenies of the parental types (SHRSP and WKY). Proneness for cerebral infarction and altered collaterals that exist in the parental SHRSP, but not the WKY, will be measured in the F1, BC and F2 progenies to test the hypothesis that these traits have a genetic etiology unrelated to the determination of the rise in BP in SHRSP. Measurements of 1) the proneness for infarction by a novel MCA occlusion test, 2) BP and 3 altered collaterals in young and adult unmedicated animals and compared to the results under drug interventions to either elevate or lower blood pressure will enable us to sort out the possible causeal relationships between an increment in BP and the traits of interest when there is evidence for close linkage. Regardless of the outcome of the cosegregation analysis, the study of the chronic drug interaction in the strains and progenies will provide valuable information of whether or not a drug induced phenotype is independent of the rat's genotype.
