To study potential central
adrenoceptor alterations in the
hypertension, we have determined alpha 1, alpha 2 and beta-
adrenoceptors using [3H]
WB4101, [3H]
yohimbine and [3H]DHA in the brain regions of spontaneously hypertensive rats (SHR),
stroke-prone SHR (SHRSP) and renal hypertensive rats. There was a significant increase in specific [3H]
WB4101 binding only in the hypothalamus of SHR and SHRSP at 16-24 weeks of age compared to that of age-matched Wistar-Kyoto rats (WKY). Scatchard analysis revealed a 28-33% increase in the Bmax value for hypothalamic [3H]
WB4101 binding without a change in the Kd value, suggesting a change in the receptor density. An increased density of alpha 1-adrenoceptors was consistently observed in the prehypertensive (5 weeks) and developmental (10 weeks) stages of spontaneous
hypertension. In contrast, there was no alpha 1-adrenoceptor alteration in the hypothalamus of rats with
renal hypertension. The receptor alteration in the SHRSP hypothalamus was not abolished by a chronic hypotensive treatment which prevented the development of
hypertension, thereby suggesting that an increased density of the alpha 1-adrenoceptors in spontaneous
hypertension does not occur secondarily to the elevation of blood pressure. The SHRSP hypothalamus showed significantly lowered levels of
noradrenaline. There was no change in specific binding of [3H]
yohimbine and [3H]DHA in the brain regions of SHRSP, except the brainstem which showed a significant decrease in the [3H]
yohimbine binding. Thus, the present study suggests an important role for hypothalamic alpha 1-adrenoceptors in the pathogenesis of spontaneous
hypertension.