De Luca Sarobe V, Nowicki S, Carranza A, Levin G, Barontini M, Arrizurieta E, Ibarra F R
Instituto de Investigaciones Médicas A. Lanari, University of Buenos Aires, Buenos Aires, Argentina.
Acta Physiol Scand. 2005 Oct;185(2):161-7. doi: 10.1111/j.1365-201X.2005.01473.x.
The interplay between natriuretic dopamine and antinatriuretic angiotensin II represents an important mechanism for the regulation of renal sodium and water excretion. Monoamine oxidase is the main metabolizing pathway for dopamine in the renal cortex. In this study, we have analysed the effect of low sodium feeding and AT1 receptor blockade on renal dopamine metabolism by monoamine oxidase.
Four groups of rats were studied: 1, normal salt diet (NS); 2, low salt diet (LS); 3, NS receiving Losartan (Los, specific AT1 receptor antagonist, 20 mg kg(-1) bwt day(-1), NS + Los); 4, LS receiving Los (LS + Los).
Urinary dopamine excretion was lower in LS than in NS rats (543 +/- 32 vs. 680 +/- 34 ng day(-1) 100 g(-1) bwt, P < 0.05). When treated with Los, DOPAC excretion and urinary DOPAC/dopamine ratio fell significantly in the LS + Los group as compared with the LS group (1199 +/- 328 vs. 3081 +/- 681 ng day(-1) 100 g(-1) bwt and 1.90 +/- 0.5 vs. 5.7 +/- 1.2, respectively, both P < 0.02). Losartan increased hydroelectrolyte excretion in the LS group. No changes were found in the NS + Los group. Aromatic L-amino acid decarboxylase activity in cortex was similar in NS and LS rats. Instead, monoamine oxidase activity was higher in cortical homogenates from LS rats (in nmol mg tissue(-1) h(-1): NS 7.66 +/- 0.52; LS 9.82 +/- 0.59, P < 0.05) and this difference was abolished in LS + Los rats (7.34 +/- 0.49 nmol mg tissue(-1) h(-1), P < 0.01, vs. LS).
We have concluded that low levels of dopamine in the urine of LS rats are because of an increase in the activity of renal monoamine oxidase and that angiotensin II mediates this increase through stimulation of AT1 receptors.
利钠性多巴胺与抗利钠性血管紧张素II之间的相互作用是调节肾钠和水排泄的重要机制。单胺氧化酶是肾皮质中多巴胺的主要代谢途径。在本研究中，我们分析了低钠饮食和AT1受体阻断对单胺氧化酶介导的肾多巴胺代谢的影响。
对四组大鼠进行研究：1，正常盐饮食（NS）；2，低钠饮食（LS）；3，接受氯沙坦（氯沙坦，特异性AT1受体拮抗剂，20mg·kg⁻¹体重·天⁻¹，NS +氯沙坦）的NS组；4，接受氯沙坦（LS +氯沙坦）的LS组。
LS组大鼠尿多巴胺排泄低于NS组（543±32对680±34ng·天⁻¹·100g⁻¹体重，P<0.05）。与LS组相比，LS +氯沙坦组用氯沙坦治疗后，3,4-二羟基苯乙酸（DOPAC）排泄和尿DOPAC/多巴胺比值显著下降（分别为1199±328对3081±681ng·天⁻¹·100g⁻¹体重和1.90±0.5对5.7±1.2，P均<0.02）。氯沙坦增加了LS组的水电解质排泄。NS +氯沙坦组未发现变化。NS组和LS组大鼠皮质中的芳香族L-氨基酸脱羧酶活性相似。相反，LS组大鼠皮质匀浆中的单胺氧化酶活性较高（以nmol·mg组织⁻¹·小时⁻¹计：NS组7.66±0.52；LS组9.82±0.59，P<0.05），而在LS +氯沙坦组大鼠中这种差异消失（7.34±0.49nmol·mg组织⁻¹·小时⁻¹，与LS组相比P<0.01）。
我们得出结论，LS组大鼠尿中多巴胺水平低是由于肾单胺氧化酶活性增加，并且血管紧张素II通过刺激AT1受体介导了这种增加。
