Intrarenal dopamine production and distribution in the rat. Physiological control of sodium excretion.
Intrarenal dopamine production and distribution in the rat. Physiological control of sodium excretion.
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大鼠肾内多巴胺的产生和分布。
DOI：
10.1161/01.hyp.29.1.228
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Carey,RM
中科院分区：
文献类型：
--
作者：
Wang,ZQ;Siragy,HM;Felder,RA;Carey,RM
多巴胺（DA）由肾近曲小管产生，已被证明是一种介导利尿和尿钠排泄的肾内旁分泌激素。 DA 发挥其细胞间作用的精确机制尚不完全清楚。在本研究中，比较了正常（0.28% NaCl，NS）或高（4.0% NaCl，HS）钠平衡状态下麻醉大鼠的肾间质液（RIF）DA（通过体内微透析）和尿 DA 排泄（UdaV）以及对急性 γ-L-谷氨酰-L-多巴（gludopa）给药的反应。 HS 大鼠的尿流量 (UV) 和钠排泄 (UnaV) 高于 NS 大鼠。与 NS 大鼠相比，HS 大鼠中 UdaV 增加。 HS 大鼠的 RIF DA 显着低于 NS 大鼠。 3、5 和 7.5 nmol/kg（静脉推注）的 Gludopa 比 RIF DA 产生更大的 UdaV 增加。只有最高剂量的鲁多巴（7.5 nmol/kg）与显着的利尿和尿钠排泄相关，该剂量导致 UdaV 增加 7.3 倍，RIF DA 增加 1.7 倍。给予格鲁多巴（7.5 nmol/kg）后，皮质和髓质血流量保持不变，而血管紧张素II（100 ng·kg−1·min−1）引起皮质和髓质血流量显着减少。先前的双侧肾去神经术对基础 DA 水平（RIF DA 和 UdaV）或鲁多巴诱导的 DA 产生或尿钠排泄和利尿没有显着影响。这些数据表明，慢性钠负荷和急性鲁多巴给药均刺激肾脏 DA 产生并主要释放到肾小管腔中，其中 DA 在控制 UnaV 方面具有直接的肾小管作用。肾脏 DA 的产生及其肾脏效应不受肾交感神经活动的显着调节。
Dopamine (DA), produced by the renal proximal tubule, has been demonstrated as an intrarenal paracrine hormone mediating diuresis and natriuresis. The precise mechanism by which DA exerts its cell-to-cell action is not fully understood. In the present study, renal interstitial fluid (RIF) DA (by in vivo microdialysis) and urinary DA excretion (UdaV) were compared in anesthetized rats on either normal (0.28% NaCl, NS) or high (4.0% NaCl, HS) sodium balance and in response to acute γ-l-glutamyl-l-dopa (gludopa) administration. Urine flow (UV) and sodium excretion (UnaV) in HS were greater than in NS rats. UdaV was increased in HS compared with NS rats. RIF DA was significantly lower in HS than NS rats. Gludopa at 3, 5, and 7.5 nmol/kg (IV bolus) produced a larger increase in UdaV than RIF DA. Only the highest dose of gludopa (7.5 nmol/kg), which resulted in a 7.3-fold increase in UdaV and 1.7-fold increase in RIF DA, was associated with significant diuresis and natriuresis. Cortical and medullary blood flow remained unchanged after gludopa (7.5 nmol/kg) administration, while angiotensin II (100 ng·kg−1·min−1) induced significant reduction in cortical and medullary blood flow. Prior bilateral renal denervation did not have a significant effect on basal DA levels (RIF DA and UdaV) or gludopa-induced DA production or natriuresis and diuresis. These data demonstrated that both chronic sodium loading and acute gludopa administration stimulated renal DA production and release predominantly into the tubule lumen, where DA had a direct tubule action in the control of UnaV. Renal DA production and its renal effects were not significantly regulated by renal sympathetic nerve activity.