Machiko Hayashi

Muscarinic cholinoceptors and choline acetyltransferase activity in the hypothalamus of spontaneously hypertensive rats

To study the role of central cholinergic mechanisms in hypertension, we have determined muscarinic receptors using [3H] (-)quinuclidinyl benzilate (QNB) and choline acetyltransferase (ChAT) activity in the brain regions of spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP) and renal hypertensive rats. The number of muscarinic receptors was significantly (33-38 %) elevated in the hypothalamus of SHR and SHRSP at the ages of 16 and 24 weeks compared to that of Wistar-Kyoto rats (WKY). An increased density of muscarinic receptors was consistently observed in the prehypertensive (5 weeks) and developmental (10 weeks) stages of hypertension. In contrast, in the hypothalamus of rats with renal hypertension there was no muscarinic receptor alteration. The receptor alteration in the SHRSP hypothalamus was not abolished by a chronic hypotensive treatment which prevented the development of hypertension, suggesting that an enhancement of the muscarinic receptors in spontaneous hypertension does not occur secondarily to the elevation of blood pressure. The hypothalamus of SHR and SHRSP at the ages of 5 and 24 weeks showed significantly less activity of ChAT. These data demonstrate that there is a specific increase in muscarinic receptors and a decrease in cholinergic activity in the hypothalamus of SHR and SHRSP. Thus, the present study suggests an important role for hypothalamic cholinergic receptors in the pathogenesis of spontaneous hypertension.

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 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.