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At least 109 records · Page 6Linked to original sources
PubMed1985

Specific increase of hypothalamic alpha 1-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.

Animals↗
PubMed1980

Hemodynamic effects on aortic enzyme activities in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHRSP and SHR) and normotensive WKR were treated with hypotensive drugs, and arterial and venous enzyme activities were compared between treated and nontreated hypertensive groups. With the 4 month experiment, cholesterol esterase activity in the aorta from hypertensive SHRSP and SHR was significantly lower than that in the respective treated groups, whereas venous activity did not differ. By contrast, aortic NAGA activity was significantly higher in the hypertensive groups without any changes in venous activity. Acid phosphatase activity was unaltered. No effects of treatment were observed in the normotensive WKR. Accompanying a decrease in aortic cholesterol esterase, there was a marked increase in aortic cholesteryl esters accompanying hypertension. Aortic phosphodiesterase activity was significantly elevated in the hypertensive SHRSP and SHR compared with the respective treated groups. These results suggest that hypertension of long duration specifically decreased aortic cholesterol esterase activity with a consequent accumulation of cholesteryl esters in the aorta, and that this hemodynamic effect seemed to be partly mediated by cyclic AMP with an effect on the lysosomal membrane. These results could provide the biochemical bases for the relationship between hypertension and atherosclerosis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1977

A cheap oral therapy for Paget's disease of bone.

Nine patients with painful Paget's disease of bone were treated for 200 days with a drug combination designed to elevated plasma calcium, hence stimulating the production of endogenous calcitoning and suppressing that of parathyroid hormone. This combination was oral calcium, a thiazide diuretic, a low phosphorus diet and aluminium hydroxide. Eight of the nine patients experienced sustained pain relief after 20--70 days. The mean plasma alkaline phosphatase (expressed as a percentage of the pre-treatment level) commenced to fall after 30 days of treatment and at 120 days was 58% of the pre-treatment level; this fall was sustained at 200 days. There was a mean rise of 0-08 mmol/l in plasma calcium; there was no significant change in plasma inorganic phosphorus or plasma creatinine. In view of the extremely low cost of this drug combination and its lack of side-effects, it is suggested it be considered as a treatment for Paget's disease of bone.

Aged↗