The responsiveness of D1- and D2-dopamine receptors in the striatum and hypothalamus of spontaneous and vasopressin hypertensive rats.

H Szmigielska, A Szmigielski, A Szadowska
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Abstract

Low doses of apomorphine (20-50 micrograms/kg) induced an increase in the activity of an endogenous inhibitor of cAMP dependent protein Kinases (type I inhibitor) in the striatum, anterior and posterior hypothalamus of normotensive rats by stimulating D2-dopamine receptors. In contrast, high doses of the compound (2-10 mg/kg) produced a dose dependent decrease in type I inhibitor activity. In the posterior hypothalamus of vasopressin hypertensive rats and SHR the maximal increase of type I inhibitor activity was markedly higher than in normotensive animals. Moreover, apomorphine induced the increase of type I inhibitor activity in a much wider range of doses. Only as high dose of the compound as 10 mg/kg was able to decrease type I inhibitor activity. This points to a marked supersensitivity of D2 receptors and suggests the subsensitivity of D1 receptors in this brain area of hypertensive rats. In contrast, in the striatum and anterior hypothalamus of hypertensive rats the apomorphine dose response curves were similar to those in normotensive rats. Thus, it seems tha hypertension is associated with the alteration in sensitivity of D2 and D1 receptors in the posterior hypothalamus, the brain area involved in regulation of blood pressure.

自发性高血压和抗利尿素高血压大鼠纹状体和下丘脑D1-和d2 -多巴胺受体的反应性。
低剂量阿波啡(20-50微克/千克)通过刺激d2 -多巴胺受体,诱导正常血压大鼠纹状体、下丘脑前部和后部的内源性cAMP依赖性蛋白激酶抑制剂(I型抑制剂)的活性增加。相反,高剂量的化合物(2- 10mg /kg)产生了剂量依赖性的I型抑制剂活性降低。抗利尿激素高血压大鼠和SHR后下丘脑I型抑制剂活性的最大增幅明显高于正常血压动物。此外,阿波啡在更大剂量范围内诱导I型抑制剂活性的增加。只有10 mg/kg的高剂量化合物才能降低I型抑制剂的活性。这表明高血压大鼠脑区D2受体明显超敏感,D1受体亚敏感。而在高血压大鼠纹状体和下丘脑前侧,阿波啡的剂量反应曲线与正常大鼠相似。因此,高血压似乎与下丘脑后部D2和D1受体敏感性的改变有关,下丘脑后部是调节血压的大脑区域。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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