内源性多巴胺和DA-1受体参与大鼠心房利钠因子的肾效应。

S S Hegde, C J Chen, M F Lokhandwala
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引用次数: 16

摘要

心房利钠因子(ANF)的利尿和利钠作用的确切机制尚不清楚。本研究旨在阐明ANF与多巴胺(DA)及DA受体相互作用在ANF对大鼠肾脏影响中的作用机制。在戊巴比妥麻醉大鼠中,ANF输注(10微克/千克/小时)产生明显的利尿和钠尿,并伴有明显的低血压、心动过缓和肾小球滤过率适度增加。然而,在ANF输注期间,尿DA排泄没有增加。用选择性DA-1受体拮抗剂SCH 23390预处理后,ANF的利尿和利钠作用明显减弱,而在SCH 23390治疗的动物中,ANF产生的血流动力学变化仍然明显。对照组和SCH 23390治疗组血浆ANF水平均升高至相同水平。多巴脱羧酶抑制剂卡比多巴预处理也显著减弱了ANF的利尿和利钠作用。SCH 23390和卡比多巴对anf诱导的利尿和钠尿的拮抗作用在程度上相当。这些结果表明,内源性DA通过激活DA-1受体,在ANF的肾效应中发挥许可作用,可能是通过增强小管对ANF的反应性。然而,似乎没有ANF对肾脏DA的产生或释放的刺激作用。
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Involvement of endogenous dopamine and DA-1 receptors in the renal effects of atrial natriuretic factor in rats.

The precise mechanism of the diuretic and natriuretic effects of Atrial Natriuretic Factor (ANF) is still unclear. The present study was undertaken with the aim of elucidating the mechanism of interaction between ANF, dopamine (DA) and DA receptors in the renal effects of ANF in rats. In pentobarbital anesthetized rats, ANF infusion (10 micrograms/kg/hour) produced marked diuresis and natriuresis which was accompanied by significant hypotension, bradycardia and also a modest increase in glomerular filtration rate. However, there was no accompanying increase in urinary DA excretion during ANF infusion. Pretreatment with SCH 23390, a selective DA-1 receptor antagonist caused significant attenuation of the diuretic and natriuretic effects of ANF whereas the hemodynamic changes produced by ANF were still evident in SCH 23390 treated animals. Plasma ANF levels were elevated to the same magnitude in both the control and SCH 23390 treated groups. Pretreatment with carbidopa, a dopa decarboxylase inhibitor also significantly blunted the diuretic and natriuretic effects of ANF. The antagonism of the ANF-induced diuresis and natriuresis by SCH 23390 and carbidopa was comparable in magnitude. These results suggest that endogenous DA, via activation of DA-1 receptors plays a permissive role in the renal effects of ANF, perhaps by enhancing tubular responsiveness to ANF. However, there does not appear to be a stimulatory effect of ANF on renal DA production or release.

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