Fedorova Olga V, Talan Mark I, Agalakova Natalia I, Lakatta Edward G, Bagrov Alexei Y
Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Circulation. 2002 Mar 5;105(9):1122-7. doi: 10.1161/hc0902.104710.
Digitalis-like sodium pump ligands (SPLs) effect natriuresis via inhibition of renal tubular Na(+),K(+)-ATPase but may induce vasoconstriction. The present study investigated the potential roles of 2 putative endogenous SPLs, an ouabain-like compound (OLC) and an alpha(1) Na(+),K(+)-ATPase inhibitor, marinobufagenin (MBG), in regulating natriuresis and blood pressure (BP) responses to sustained and acute NaCl loading in Dahl salt-sensitive rats (DS).
During 4 weeks of an 8% NaCl diet, DS exhibited a progressive increase in MBG renal excretion (66 +/-13 pmol/24 hours at week 4 versus 11 +/- 1 pmol/24 hours at baseline, n=48), which paralleled an increase in systolic BP (174 +/- 10 mm Hg at week 4 versus 110 +/- 2 mm Hg at baseline). By contrast, OLC excretion peaked at week 1 and returned to baseline levels. Administration of an anti-MBG, but not anti-ouabain antibody, to DS after 3 weeks of a high NaCl diet lowered BP (139 +/- 7 versus 175 +/- 5 mm Hg, P<0.001, n=5). Acute NaCl loading (2 hours) of DS (n=5) increased MBG and OLC excretion and natriuresis. Pretreatment of acutely NaCl-loaded DS with an anti-MBG antibody (n=5) reduced the excretion of sodium and MBG but not that of OLC. An anti-ouabain antibody (n=5) reduced sodium excretion and both OLC and MBG.
An initial transient stimulation of OLC induced by NaCl loading of DS precedes an MBG response. A sustained increase in MBG production in DS contributes to the chronic BP elevation induced by a sustained high NaCl intake.
洋地黄样钠泵配体（SPLs）通过抑制肾小管钠钾ATP酶发挥利钠作用，但可能会引起血管收缩。本研究调查了两种假定的内源性SPLs，一种哇巴因样化合物（OLC）和一种α1钠钾ATP酶抑制剂，海蟾蜍精（MBG），在调节Dahl盐敏感大鼠（DS）对持续性和急性氯化钠负荷的利钠及血压（BP）反应中的潜在作用。
在8%氯化钠饮食的4周期间，DS的MBG肾排泄量逐渐增加（第4周为66±13 pmol/24小时，而基线时为11±1 pmol/24小时，n = 48），这与收缩压升高相平行（第4周为174±10 mmHg，而基线时为110±2 mmHg）。相比之下，OLC排泄量在第1周达到峰值，然后恢复到基线水平。在高盐饮食3周后给DS注射抗MBG抗体而非抗哇巴因抗体可降低血压（139±7 mmHg对175±5 mmHg，P<0.001，n = 5）。对DS（n = 5）进行急性氯化钠负荷（2小时）可增加MBG和OLC排泄以及利钠作用。用抗MBG抗体预处理急性氯化钠负荷的DS（n = 5）可减少钠和MBG的排泄，但不能减少OLC的排泄。抗哇巴因抗体（n = 5）可减少钠排泄以及OLC和MBG的排泄。
DS氯化钠负荷诱导的OLC初始短暂刺激先于MBG反应。DS中MBG产生的持续增加导致持续高盐摄入引起的慢性血压升高。
