外源性多巴胺对肾脏的影响：肾神经及多巴胺受体拮抗剂的调节作用
Renal effects of exogenous dopamine: modulation by renal nerves and dopamine receptor antagonists.
作者信息
Luippold G, Osswald H, Mühlbauer B
机构信息
Department of Pharmacology, University of Tübingen, Germany.
出版信息
Naunyn Schmiedebergs Arch Pharmacol. 1998 Oct;358(4):445-51. doi: 10.1007/pl00005277.
The modulation of the renal response to exogenous dopamine by renal denervation (DNX) and dopamine receptor antagonists was investigated in thiopental-anesthetized Sprague-Dawley rats. Experiments were performed after reaching stable systemic hemodynamics and urinary flow rate. These conditions were obtained with an infusion rate of approximately 1.2% of body weight per hour. In the vehicle group (VHC) i.v. infusion of dopamine (1, 3 and 9 microg kg(-1) min(-1) significantly increased glomerular filtration rate (GFR), assessed by renal clearance of [3H]inulin, by 14+/-1.5, 16+/-1.6 and 31+/-2.6%, respectively. Infusion of 1 and 3 microg kg(-1) min(-1) dopamine did not change systemic hemodynamics while the highest dose elevated heart rate, potentially contributing to the GFR increase. The specific D1 receptor antagonist SCH 23390 (10 microg kg(-l) min(-1) i.v.) did not affect the GFR response to dopamine infusion. In contrast, domperidone (DOM; 8 microg kg(-1) min(-1) i.v.), a specific, peripherally acting D2 antagonist, attenuated the glomerular hyperfiltration induced by the three doses of dopamine to 11+/-1.7, 13+/-2.2 and 16+/-2.6%, respectively. DNX diminished the GFR response to dopamine infusion to almost the same extent (11+/-2.8, 10+/-2.2 and 17+/-2.6%, respectively) as did DOM. When DNX animals were treated with DOM, the GFR responses to dopamine were further attenuated to non-significant increases. These additive effects of DOM and DNX suggest that two different mechanisms are involved. Both DNX and SCH 23390 decreased sodium excretion at baseline whereas DOM enhanced it. Under the present experimental condition, neither D1 nor D2 receptor blockade affected the natriuretic and diuretic response to dopamine. Whereas D1 receptors do not appear to be involved, both D2 receptors and renal nerves play a role in the renal hemodynamic response to dopamine, indicating involvement of both pre- and postsynaptical dopamine receptors.
在硫喷妥钠麻醉的Sprague-Dawley大鼠中，研究了肾去神经支配（DNX）和多巴胺受体拮抗剂对外源性多巴胺肾脏反应的调节作用。在达到稳定的全身血流动力学和尿流率后进行实验。这些条件通过以每小时约1.2%体重的输注速率获得。在载体组（VHC）中，静脉输注多巴胺（1、3和9μg kg⁻¹ min⁻¹）显著增加了肾小球滤过率（GFR），通过[³H]菊粉的肾脏清除率评估，分别增加了14±1.5%、16±1.6%和31±2.6%。输注1和3μg kg⁻¹ min⁻¹多巴胺未改变全身血流动力学，而最高剂量升高了心率，这可能是GFR增加的原因。特异性D1受体拮抗剂SCH 23390（10μg kg⁻¹ min⁻¹静脉注射）不影响多巴胺输注引起的GFR反应。相反，多潘立酮（DOM；8μg kg⁻¹ min⁻¹静脉注射），一种特异性的外周作用D2拮抗剂，将三剂量多巴胺诱导的肾小球超滤分别减弱至11±1.7%、13±2.2%和16±2.6%。DNX将多巴胺输注引起的GFR反应减弱到与DOM几乎相同的程度（分别为11±2.8%、10±2.2%和17±2.6%）。当用DOM治疗DNX动物时，多巴胺引起的GFR反应进一步减弱至无显著增加。DOM和DNX的这些相加作用表明涉及两种不同的机制。DNX和SCH 23390在基线时均降低钠排泄，而DOM增强钠排泄。在本实验条件下，D1或D2受体阻断均不影响对多巴胺的利钠和利尿反应。虽然D1受体似乎不参与，但D2受体和肾神经在对多巴胺的肾脏血流动力学反应中均起作用，表明突触前和突触后多巴胺受体均参与其中。
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