Sigetomi S, Fukuchi S
Department of Internal Medicine III, Fukushima Medical College.
Nihon Naibunpi Gakkai Zasshi. 1993 Oct 20;69(9):953-62. doi: 10.1507/endocrine1927.69.9_953.
Dopamine has been well recognized to be a precursor of norepinephrine, exhibiting cardiovascular effects through alpha-adrenoceptor stimulation by norepinephrine production and release in sympathetic nerve endings. It also has the specific and unique effects of natriuresis and vasodilation. Since dopamine is one of the important endogenous hypotensive and natriuretic substances, it is speculated that impaired dopamine generation and/or the disturbance of the effects of dopamine could cause hypertension with suppression of plasma renin activity and/or salt-sensitivity. A non-specific enzyme of aromatic L-amine acid decarboxylase (AAAD) converting from 3,4-dihydroxyphenylalanine (DOPA) to dopamine is widely distributed in the peripheral tissue, e.g. the sympatho-adrenomedullary system, the small intestine, the lung, the liver, the kidney, etc. Since tyrosine hydroxylase is a rate-limiting enzyme of catecholamine biosynthesis, DOPA generation in the neuronal tissues is accelerated with the sympathetic nerve activation by stress such as emotional and environmental changes, resulting in an increase of DOPA delivery to the non-neuronal tissues containing non-neuronal AAAD. More than five receptors for dopamine are cloned in the brain, and it is suggested that more than three different types of dopamine receptors are in the peripheral tissues. In spontaneously hypertensive rats, the post-receptor defect of renal dopamine D1-receptor has been proposed where peripheral dopamine generation compensatorily increased. In Dahl salt-sensitive rats, another model of genetic hypertension, the blunted response of urinary dopamine to sodium loading has been demonstrated. It is controversial whether abnormalities of the neuronal and/or non-neuronal (particularly renal) dopamine system play a contributory role on the pathogenesis of essential hypertension. However, it is plausible that the impairment of dopamine generation and/or the defective responses of a dopamine receptor might induce sodium retention and hypertension.
多巴胺一直被公认为去甲肾上腺素的前体,它通过去甲肾上腺素在交感神经末梢的产生和释放,刺激α-肾上腺素能受体,从而产生心血管效应。它还具有利钠和血管舒张的特定独特作用。由于多巴胺是重要的内源性降压和利钠物质之一,因此推测多巴胺生成受损和/或多巴胺效应紊乱可能导致高血压,并伴有血浆肾素活性抑制和/或盐敏感性。一种将3,4-二羟基苯丙氨酸(DOPA)转化为多巴胺的非特异性芳香族L-氨基酸脱羧酶(AAAD)广泛分布于外周组织,如交感-肾上腺髓质系统、小肠、肺、肝、肾等。由于酪氨酸羟化酶是儿茶酚胺生物合成的限速酶,在情绪和环境变化等应激引起交感神经激活时,神经元组织中DOPA的生成会加速,导致输送到含有非神经元AAAD的非神经元组织中的DOPA增加。在大脑中已克隆出五种以上的多巴胺受体,提示外周组织中存在三种以上不同类型的多巴胺受体。在自发性高血压大鼠中,有人提出肾多巴胺D1受体存在受体后缺陷,外周多巴胺生成会代偿性增加。在另一种遗传性高血压模型——Dahl盐敏感大鼠中,已证实尿多巴胺对钠负荷的反应迟钝。神经元和/或非神经元(特别是肾脏)多巴胺系统异常是否在原发性高血压发病机制中起作用仍存在争议。然而,多巴胺生成受损和/或多巴胺受体反应缺陷可能导致钠潴留和高血压,这是有道理的。