Changes in catecholamine neuronal uptake and receptor binding in the brains of spontaneously hypertensive rats (SHR)

In these studies we have characterized differences between spontaneously hypertensive rats (SHR) and normotensive Wistar/Kyoto (WKY) rats with respect to rates of neuronal uptake of norepinephrine (NE) and dopamine (DA), and beta-adrenergic receptor (dihydroalprenolol; [3H]DHA) binding in the central nervous system. We find that SHR have greater rates of NE uptake in the frontal cortex, cerebellum, hypothalamus and pons-medulla during early development, and that these changes are accounted for, at least in the cerebral cortex, by an increased Vmax of the NE uptake mechanism. In addition, we find a decrease in the Bmax for [3H]DHA binding, suggestive of down-regulation of beta-adrenergic receptors of this region. In contrast to the results for NE uptake, we have measured significant decreases in DA uptake in the frontal cortex of the SHR at several postnatal ages. Decreases in DA uptake were also observed in the striatum of SHR although these changes were found only in animals approximately 6 weeks of age. From these results we have suggested that NE neurons projecting to a number of brain regions have elevated functional activity, while more regionally selective decreases in dopaminergic functional activity are characteristic of the SHR. We have further proposed that these changes in catecholamine neurons of the central nervous system may play an important role in the development of both the hypertension and behavioral hyperactivity exhibited by these animals.