Dantonello T M, Küster E, Mühlbauer B
Department of Pharmacology, Medical Faculty, University of Tübingen, Germany.
Kidney Blood Press Res. 1998;21(6):438-44. doi: 10.1159/000025897.
A defective renal dopaminergic system has been suggested to contribute, via impaired sodium excretion, to the pathogenesis of hypertension. Data according renal dopamine (DA) release in hypertension, however, are inconsistent. In the present study, we compared urinary DA excretion (UDAV), plasma free DA (PDA), and renal tissue DA contents (TDA) of young spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats. Since the protein intake dominantly controls UDAV, fasted animals were used to exclude the influence of feeding. Conscious WKY and SHR had a similar UDAV which was lower compared to SD rats. Thiopental anesthesia increased UDAV in SHR and WKY but not in SD rats. TDA was higher in SHR compared to SD and WKY rats. To investigate the tubular capacity to generate DA, the response to L-DOPA infusion was assessed in two doses. 1 nmol/min/100 g body weight L-DOPA increased UDAV approximately 30-fold in all strains but did not affect tubular sodium excretion or renal hemodynamics. In contrast, infusion of 3 micromol/min/100 g body weight L-DOPA increased UDAV by five orders of magnitude and induced natriuresis, diuresis, and tachycardia. These effects were assigned to an increase in PDA and no significant differences were observed among the strains. We conclude that, regarding renal DA, (1) the differences among SHR, WKY, and SD rats rather appear to be strain related than hypertension associated; (2) the renal capacity of DA generation from L-DOPA is not impaired in SHR; (3) tubular DA at physiological concentrations does not alter sodium excretion significantly in normo- or hypertensive rats, and (4) the influence of anesthesia on UDAV should be considered in comparative studies.
有研究表明，肾脏多巴胺能系统缺陷通过损害钠排泄，参与高血压的发病机制。然而，关于高血压患者肾脏多巴胺（DA）释放的数据并不一致。在本研究中，我们比较了年轻自发性高血压大鼠（SHR）、Wistar-Kyoto（WKY）大鼠和Sprague-Dawley（SD）大鼠的尿DA排泄量（UDAV）、血浆游离DA（PDA）和肾组织DA含量（TDA）。由于蛋白质摄入对UDAV起主要控制作用，因此使用禁食动物以排除进食的影响。清醒的WKY和SHR的UDAV相似，均低于SD大鼠。硫喷妥钠麻醉可增加SHR和WKY的UDAV，但对SD大鼠无此作用。与SD和WKY大鼠相比，SHR的TDA更高。为了研究肾小管生成DA的能力，评估了两种剂量的L-DOPA输注反应。1 nmol/min/100 g体重的L-DOPA可使所有品系的UDAV增加约30倍，但不影响肾小管钠排泄或肾血流动力学。相比之下，输注3 μmol/min/100 g体重的L-DOPA可使UDAV增加5个数量级，并诱导利钠、利尿和心动过速。这些作用归因于PDA的增加，各品系之间未观察到显著差异。我们得出结论，关于肾脏DA，（1）SHR、WKY和SD大鼠之间的差异似乎与品系有关，而非与高血压相关；（2）SHR中由L-DOPA生成DA的肾脏能力未受损；（3）生理浓度的肾小管DA在正常或高血压大鼠中不会显著改变钠排泄；（4）在比较研究中应考虑麻醉对UDAV的影响。
