Mühlbauer B, Hartenburg E, Osswald H
Pharmakologisches Institut, Universität Tübingen, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1994 Mar;349(3):244-9. doi: 10.1007/BF00169290.
Previously, we have found that feeding is a dominant factor controlling urinary dopamine excretion (UDA) in conscious rats (Mühlbauer and Osswald 1992). Since the renal response to feeding is also characterized by an increase in glomerular filtration rate (GFR), we wanted to investigate in a first step whether the feeding-induced elevations of GFR and UDA could be causally related phenomena. Therefore, we studied the influence of dopamine synthesis and dopamine receptor blockade on the renal response to amino acid infusion (AA) in thiopental anesthetized rats. AA infusion (n = 7) increased GFR by 33 +/- 7% (P < 0.001) and UDA by 87 +/- 19% (P < 0.001). In the presence of benserazide (BZD, n = 5), an inhibitor of dopamine synthesis, infused i.v. at a dose of 30 micrograms/min/kg, UDA was suppressed to values below detection limit and the AA-induced GFR increase was abolished. Continuous intravenous infusion of the DA1 receptor antagonist SCH 23390 (SCH, n = 7) in a dose of 4.0 micrograms/kg/min did not prevent the AA-induced increase in GFR (33 +/- 3%, P < 0.001) and UDA (97 +/- 12%, P < 0.001). In contrast, S-sulpiride (SUL), a specific DA2 receptor antagonist, infused continuously i.v. in a dose of 5 micrograms/kg/min, completely abolished the AA-induced GFR increase, while UDA was increased 1.6-fold (P < 0.01). Like BZD, both dopamine receptor antagonists did not affect renal sodium excretion substantially. Our results suggest, that endogenous dopamine could act as a mediator in the renal response to amino acid infusion in the rat, most likely by activation of DA2 receptors.
此前，我们已发现进食是控制清醒大鼠尿多巴胺排泄（UDA）的主要因素（米尔鲍尔和奥斯瓦尔德，1992年）。由于肾脏对进食的反应也表现为肾小球滤过率（GFR）增加，我们想在第一步研究进食诱导的GFR和UDA升高是否可能是因果相关的现象。因此，我们研究了多巴胺合成和多巴胺受体阻断对硫喷妥钠麻醉大鼠氨基酸输注（AA）后肾脏反应的影响。AA输注（n = 7）使GFR增加33±7%（P < 0.001），UDA增加87±19%（P < 0.001）。在静脉注射剂量为30微克/分钟/千克的多巴胺合成抑制剂苄丝肼（BZD，n = 5）时，UDA被抑制到检测限以下，且AA诱导的GFR增加被消除。以4.0微克/千克/分钟的剂量持续静脉输注DA1受体拮抗剂SCH 23390（SCH，n = 7）并不能阻止AA诱导的GFR增加（33±3%，P < 0.001）和UDA增加（97±12%，P < 0.001）。相比之下，以5微克/千克/分钟的剂量持续静脉输注特异性DA2受体拮抗剂S-舒必利（SUL），完全消除了AA诱导的GFR增加，而UDA增加了1.6倍（P < 0.01）。与BZD一样，两种多巴胺受体拮抗剂对肾钠排泄基本没有影响。我们的结果表明，内源性多巴胺可能在大鼠对氨基酸输注的肾脏反应中起介导作用，很可能是通过激活DA2受体。
