Quantitative immunohistochemical distributions of tyrosine hydroxylase and calmodulin in the brains of spontaneously hypertensive rats.

Abstract

Immunohistochemical distributions of tyrosine hydroxylase and calmodulin in the rat forebrain were analyzed quantitatively as a possible model for the hypertension mechanism. The brain slices of spontaneously hypertensive rats (SHR) at 12 weeks of age were stained immunohistochemically for tyrosine hydroxylase and for calmodulin, and the distributions and amounts of these proteins were measured at 40-microns intervals by a fluorescence microphotometry system in comparison with those in normotensive control, Wistar Kyoto rats (WKY, the parent strain of SHR). Tyrosine hydroxylase levels in the neostriatum, nucleus accumbens, nucleus septi lateralis and tractus diagonalis, and calmodulin levels in the medial part of the neostriatum of SHR were lower than those in WKY. We reported previously that the decrease of the serum calcium level in SHR causes a decrease of the dopamine levels in the neostriatum and nucleus accumbens regions through a calmodulin-dependent system, and subsequent low levels of dopamine in the brain which may produce an increase in blood pressure. Combining this finding and our previous reports, we also suggest that the lower dopamine levels seen in the neostriatum and nucleus accumbens regions of SHR may result from the decrease in tyrosine hydroxylase and/or calmodulin levels in these regions in addition to the abnormality of calcium metabolism, and low levels of dopamine may produce an increase in blood pressure through functions of cerebral dopaminergic neurons and peripheral sympathetic nerves.