Alvelos Margarida, Ferreira António, Bettencourt Paulo, Pimenta Joana, Azevedo Ana, Serrão Paula, Rocha-Gonçalves Francisco, Soares-da-Silva Patrício
Unit of Cardiovascular Research and Development, University of Porto Medical School, Porto, Portugal.
J Cardiovasc Pharmacol. 2005 Mar;45(3):197-203. doi: 10.1097/01.fjc.0000152032.46373.e7.
Dopamine of renal origin has natriuretic/diuretic actions by activating D1-like receptors of the nephron. Saline load increases renal dopamine production and natriuresis in healthy subjects, and, under these conditions, the activation of D2-like receptors also produces natriuresis/diuresis. Metoclopramide is a D2-like receptor antagonist. Patients with heart failure (HF) have an increased renal dopamine-synthesizing efficiency. However, the effect of salt loading was not explored in HF. We hypothesized that HF patients respond to salt loading with increased production of renal dopamine and that metoclopramide antagonizes this response. This was a randomized, controlled, crossover study exploring the effect of NaCl and metoclopramide on renal dopaminergic, sympathetic, renin-angiotensin-aldosterone, and arginine-vasopressin (AVP) systems activity on sodium handling in 9 HF patients and 9 controls. NaCl markedly increased renal dopamine production and natriuresis in both groups. Metoclopramide blunted these responses in HF patients but not in controls. NaCl decreased renin and aldosterone plasma levels in controls but not in HF patients. In these patients B-type natriuretic peptide (BNP) levels increased, but AVP was not affected. HF patients respond to salt loading with increased natriuresis. However, the mechanisms for this response are different from those found in healthy subjects. Metoclopramide has antinatriuretic effects only in HF patients.
肾源性多巴胺通过激活肾单位的 D1 样受体发挥利钠/利尿作用。在健康受试者中，盐负荷可增加肾多巴胺生成及利钠作用，且在此情况下，D2 样受体的激活也可产生利钠/利尿作用。甲氧氯普胺是一种 D2 样受体拮抗剂。心力衰竭（HF）患者肾多巴胺合成效率增加。然而，尚未在 HF 患者中探究盐负荷的影响。我们假设 HF 患者对盐负荷的反应是肾多巴胺生成增加，且甲氧氯普胺可拮抗这一反应。这是一项随机、对照、交叉研究，旨在探究氯化钠和甲氧氯普胺对 9 例 HF 患者和 9 例对照者肾多巴胺能、交感神经、肾素 - 血管紧张素 - 醛固酮及精氨酸加压素（AVP）系统活性以及钠处理的影响。氯化钠显著增加了两组患者的肾多巴胺生成及利钠作用。甲氧氯普胺减弱了 HF 患者的这些反应，但对对照者无此作用。氯化钠降低了对照者血浆肾素和醛固酮水平，但对 HF 患者无此作用。在这些患者中，B 型利钠肽（BNP）水平升高，但 AVP 未受影响。HF 患者对盐负荷的反应是利钠增加。然而，这种反应的机制与健康受试者不同。甲氧氯普胺仅在 HF 患者中具有抗利钠作用。
