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Summary
Spontaneously hypertensive rats (SHR), which are normotensive at birth and develop sustained hypertension between 3 and 6 months of age, are the model most extensively investigated for evaluating hypertensive brain damage and its treatment. The timedependent rise of arterial blood pressure and the occurrence of brain atrophy, loss of nerve cells and glial reaction are shared to some extent with what occurs human hypertensive brain. SHR, therefore, can represent a reasonable model of hypertensionrelated brain damage. Our main studies on cerebrovascular and brain microanatomical changes occurring in SHR and their sensitivity to pharmacological interventions are summarized.
Key words
Hypertension, brain damage, experimental model
Spontaneously hypertensive rats (SHR), which are normotensive at birth and develop in the fi rst 6 months of life a sustained hypertension, currently represent the best model of essential hypertension allowing for the investigation of causes, mechanisms and pathology of hypertension (Amenta et al., 2003).
In SHR brain, ventricular enlargement, accompanied by loss of brain tissue and brain weight, and decrease in volume of grey matter have been reported (Tajima et al., 1993; Lanari et al., 2007). In 6 to 7monthold SHR, the ventricular volume is twofold greater than in WistarKyoto (WKY) control rats. The volume of the entire brain and of different gray matter areas as well as the thickness of cerebral cortex are 1125% less in SHR (Fig. 1, AD) than in wild type animals. The hippocampus, a key area for learning and memory, is smaller in 6monthold SHR than in normotensive cohorts (Sabbatini et al., 2002), and the same is true for the density of cell nuclei in the dentate gyrus subfi eld in SHR aged 67 months (Tajima et al., 1993) (Fig. 1, E, F).
Cerebrovascular alterations characterized by blood vessel wall hypertrophy or remodeling are closely related to the degree of blood pressure elevation. Hypertrophy consists in thickening of arterial wall with decrease of internal diameter, increase of external diameter and consequent reduction of lumen size. Remodeling consists of smooth muscle rearrangement with decrease of external and internal diameters and of lumen size (Amenta et al., 2003). These changes cause an increase of the walltolumen ratio and consequently of arterial resistance. In the frontal cortex of 24weeksold SHR the vascular tree displayed wall hypertrophy...