Early breakdown of dendritic bundles in the retrosplenial granular cortex of hypertensive rats: prevention by antihypertensive therapy.

Layer II pyramidal neurons in retrosplenial granular cortex (Rg) give rise to apical dendrites that bundle together tightly in layer Ic and Ib and spread out in layer Ia, where they arborize extensively. These dendritic bundles in Rg become disorganized in very old rats. Since hypertensive rats appear to age more rapidly than normotensive rats, we tested the hypothesis that the disorganization of the dendritic bundles in layer I of Rg is present at a much earlier age in hypertensive rats [spontaneously hypertensive rats (SHR)] compared to normotensive rats [Sprague-Dawley rats (SD)]. Further, we tested the hypothesis that long-term, antihypertensive drug treatment (captopril) prevents or attenuates the breakdown of the dendritic bundles in Rg of SHR. The retrograde tracer Fluorogold was injected into Rg to document the morphology of the apical dendrites of the layer II Rg neurons. In 4-month-old SD and SHR, most densely labeled layer II neurons have labeled apical dendrites that are confined to the dendritic bundles in layer Ib and Ic, and these dendrites arborize extensively only in layer Ia of Rg. In 14-month-old SD this pattern is preserved, but in contrast, in 14-month-old SHR most of the labeled apical dendrites lie outside the bundles, and less than half these dendrites reach layer Ia. Chronic antihypertensive therapy significantly attenuates this disorganization in 14-month-old SHR. These data indicate that in SHR, the layer II neurons in Rg are highly vulnerable to the combined effects of hypertension and aging, and the results suggest that hypertension is a primary contributor to these structural alterations.