Szmigielska H, Szmigielski A, Szadowska A
Department of Pharmacodynamics, Medical Academy, Lódź, Poland.
Pol J Pharmacol Pharm. 1992 Jul-Aug;44(4):355-64.
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.
低剂量的阿扑吗啡（20 - 50微克/千克）通过刺激D2 - 多巴胺受体，使正常血压大鼠纹状体、下丘脑前部和后部中一种内源性环磷酸腺苷依赖性蛋白激酶抑制剂（I型抑制剂）的活性增加。相比之下，高剂量的该化合物（2 - 10毫克/千克）使I型抑制剂活性呈剂量依赖性降低。在血管升压素性高血压大鼠和自发性高血压大鼠（SHR）的下丘脑后部，I型抑制剂活性的最大增加明显高于正常血压动物。此外，阿扑吗啡在更广泛的剂量范围内诱导I型抑制剂活性增加。只有高达10毫克/千克的高剂量该化合物才能降低I型抑制剂活性。这表明高血压大鼠该脑区的D2受体存在明显超敏反应，并提示D1受体存在低敏反应。相比之下，在高血压大鼠的纹状体和下丘脑前部，阿扑吗啡的剂量反应曲线与正常血压大鼠相似。因此，似乎高血压与参与血压调节的脑区下丘脑后部中D2和D1受体敏感性的改变有关。
