ATTENUATED RENAL RESPONSE TO DOPAMINERGIC DRUGS IN SPONTANEOUSLY HYPERTENSIVE RATS
ATTENUATED RENAL RESPONSE TO DOPAMINERGIC DRUGS IN SPONTANEOUSLY HYPERTENSIVE RATS
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DOI：
10.1161/01.hyp.15.6.560
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发表时间：
1990-06-01
期刊：
影响因子：
8.3
通讯作者：
JOSE, PA
中科院分区：
文献类型：
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作者：
FELDER, RA;SEIKALY, MG;JOSE, PA
肾多巴胺-1受体的激活降低钠转运。然而，自发性高血压大鼠保留钠，尽管增加肾脏多巴胺浓度。我们通过研究高血压大鼠和血压正常的Wistar-Kyoto大鼠肾内输注多巴胺-1激动剂SKF-38393和多巴胺-1拮抗剂SCH-23390的影响，检验了自发性高血压大鼠（Okamoto-Aoki品系）钠处理异常与多巴胺能反应降低相关的假设。在戊巴比妥麻醉下研究肾神经完整的大鼠（9-16周龄）（每组n = 5-6）。验证了SKF-38393的多巴胺-1效应的特异性，因为多巴胺-1拮抗剂SCH-23390（n = 5）以剂量相关方式阻断了其利钠作用。肾动脉内输注多巴胺-1激动剂SKF-38393不影响肾小球滤过率，但在血压正常的大鼠中导致剂量相关的尿钠排泄和利尿，但在高血压大鼠中则不然。多巴胺-1拮抗剂SCH-23390单独肾动脉内输注诱导抗尿性白蛋白尿，而不影响肾小球滤过率，在正常血压，但不高血压大鼠。在多巴胺-1拮抗剂输注液中加入多巴胺-1拮抗剂YM-09151不会增强多巴胺-1拮抗剂的作用。在高血压大鼠中缺乏对多巴胺-1激动剂或拮抗剂的反应不是由于肾多巴胺-1受体密度的差异（1.3 ± 0.01）。0.3对于自发性高血压大鼠，n = 4; 1 . ±. 0.2对于Wistar-Kyoto大鼠，n = 4）或亲和力;放射自显影法测定的分布也相似。9-16周龄自发性高血压大鼠肾脏钠处理异常的部分原因是多巴胺-1受体远端反应降低。
Activation of renal dopamine-1 receptors decreases sodium transport. However, the spontaneously hypertensive rat retains sodium despite increased renal dopamine concentration. We tested the hypothesis that the abnormal sodium handling in spontaneously hypertensive rats (Okamoto-Aoki strain) is related to a decreased dopaminergic response by studying the effects of the intrarenal infusion of the dopamine-1 agonist SKF-38393 and the dopamine-1 antagonist SCH-23390 in hypertensive and in normotensive Wistar-Kyoto rats. Rats (9-16 weeks old) were studied with renal nerves intact under pentobarbital anesthesia (n = 5-6 in each group). Specificity of dopmaine-1 effects of SKF-38393 was verified because its natriuretic effect was blocked in a dose-related manner by the dopamine-1 antagonist SCH-23390 (n = 5). Intrarenal arterial infusion of the dopamine-1 agonist SKF-38393 did not affect glomerular filtration rate but resulted in a dose-related natriuresis and diuresis in normotensive but not in hypertensive rats. Intrarenal arterial infusion of the dopamine-1 antagonist SCH-23390 alone induced an antinatriuresis, without affecting glomerular filtration rate, in normotensive but not in hypertensive rats. Addition of the dopamine-1 antagonist YM-09151 to the dopamine-1 antagonist infusion did not enhance the effect of the dopamine-1 antagonist. The lack of response to the dopamine-1 agonist or antagonist in hypertensive rats was not due to differences in renal dopamine-1 receptor density (1.3 .+-. 0.3 pmol/mg protein for spontaneously hypertensive rats, n = 4; 1 .+-. 0.2 for Wistar-Kyoto rats, n = 4) or affinity; distribution determined by autoradiography was also similar. The abnormal renal sodium handling in 9-16-week-old spontaneously hypertensive rats is in part due to decreased response distal to the dopamine-1 receptor.