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(Hypertension. 1999;33:681-685.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Genetic and Gender Influences on Sensitivity to Focal Cerebral Ischemia in the Stroke-Prone Spontaneously Hypertensive Rat

Hilary V. O. Carswell; Niall H. Anderson; James S. Clark; Delyth Graham; Baxter Jeffs; Anna F. Dominiczak; I. Mhairi Macrae

From the Wellcome Surgical Institute (H.V.O.C., I.M.M.), Department of Statistics (N.H.A.), and Department of Medicine and Therapeutics (N.H.A., J.S.C., D.G., B.J., A.F.D.), University of Glasgow (Scotland, UK).

Correspondence to Hilary Carswell, Wellcome Surgical Institute, University of Glasgow, Glasgow, G61 1QH, Scotland, UK. E-mail hvo1a{at}udcf.gla.ac.uk

Abstract—We have investigated genetic transmission of increased sensitivity to focal cerebral ischemia and the influence of gender in the stroke-prone spontaneously hypertensive rat (SHRSP). Halothane-anesthetized, 3- to 5-month-old male and female Wistar-Kyoto rats (WKY), SHRSP, and the first filial generation rats (F₁ crosses 1 and 2) underwent distal (2 mm) permanent middle cerebral artery occlusion (MCAO) by electrocoagulation. Infarct volume was measured by using hematoxylin-eosin–stained sections and image analysis 24 hours after ischemia and expressed as a percentage of the volume of the ipsilateral hemisphere. Infarct volume in males and females grouped together were significantly larger in SHRSP, F₁ cross 1 (SHRSP father), and F₁ cross 2 (WKY father), at 36.6±2.3% (mean±SEM, P<0.001, n=15), 25.4±2.4% (P<0.01, n=14), and 33.9±1.6% (P<0.001, n=18), respectively, compared with WKY (14±2%, n=17). Male F₁ cross 1 (18.9±2.4%, n=6) developed significantly smaller infarcts than male F₁ cross 2 (32.8±2%, n=8, P<0.005). Females, which underwent ischemia during metestrus, developed larger infarcts than respective males. A group of females in which the cycle was not controlled for developed significantly smaller infarcts than females in metestrus. Thus, the increased sensitivity to MCAO in SHRSP is retained in both F₁ cross 1 and cross 2 hybrids, suggesting a dominant or codominant trait; response to cerebral ischemia appears to be affected by gender and stage in the estrous cycle. In addition, the male progenitor of the cross (ie, SHRSP versus WKY) influences stroke sensitivity in male F₁ cohorts.

Key Words: rats, stroke-prone spontaneously hypertensive • cerebral ischemia, focal • gender • estrus • estrogen • middle cerebral artery occlusion

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