Specific increase of hypothalamic α1-adrenoceptors in spontaneously hypertensive rats: Effect of hypotensive drug treatment

To study potential central adrenoceptor alterations in the hypertension, we have determined α₁, α₂ and β-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 B_max value for hypothalamic [³H]WB4101 binding without a change in the K_d value, suggesting a change in the receptor density. An increased density of α₁-adrenoceptors was consistently observed in the prehypertensive (5 weeks) and developmental (10 weeks) stages of spontaneous hypertension. In contrast, there was no α₁-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 α₁-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 α₁-adrenoceptors in the pathogenesis of spontaneous hypertension.