Endogenous Na,K pump ligands are differentially regulated during acute NaCl loading of Dahl rats.
Endogenous Na,K pump ligands are differentially regulated during acute NaCl loading of Dahl rats.
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Dahl 大鼠急性 NaCl 负荷期间，内源 Na、K 泵配体受到差异性调节。
DOI：
10.1161/01.cir.102.24.3009
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发表时间：
2000
期刊：
影响因子：
37.8
通讯作者：
Bagrov,AY
中科院分区：
文献类型：
--
作者：
Fedorova,OV;Lakatta,EG;Bagrov,AY
背景：两种类似洋地黄的哺乳动物因子，一种类似瓦阿拜碱的化合物（OLC）和一种marinobufagenin (MBG)，分别对α-3和α-1 Na+，K+- atp酶亚型具有特异性。我们比较了急性NaCl负荷对Dahl盐敏感（DS）和耐盐（DR）大鼠MBG和OLC的调节。方法与结果：对成年雄性大鼠（24只DS、24只DR）腹腔灌胃0.8 g/kg的NaCl。测量利尿、尿钠、肾排泄及组织内MBG和OLC水平。比较MBG和乌阿班对DS、DR和Wistar大鼠肾Na+、K+- atp酶的抑制作用。DS（与DR相比）表现出较小的峰值（2小时）尿钠反应（1.34±0.10 vs 2.08±0.14 mmol·kg - 1·h - 1， P<0.01），尽管血浆Na+更高（153±2 vs 145±1 mmol/L， P<0.01）。在DS和DR中，垂体、肾上腺和血浆OLC表现出短暂的2- 3倍增加，随后下降到基线水平。两种菌株的血浆和肾上腺MBG在NaCl加载1小时内增加了一倍，并保持升高。DS组8小时MBG排泄量是DR组的4倍（15.8±0.8 pmol vs 3.6±0.4 pmol， P<0.01），而DS组OLC排泄量仅比DR组高30%（16.1±1.1 pmol vs 11.9±0.8 pmol， P<0.05）。Wistar大鼠和DS肾Na+，K+- atp酶（α-1亚型）对MBG的敏感性高于对瓦巴因的敏感性。结论：nacl加载DS可导致OLC短暂升高，但MBG组织水平和排泄量持续升高。我们假设MBG的产生增加是为了补偿遗传受损的压力-钠尿机制。
Background—Two mammalian digitalis-like factors, an ouabain-like compound (OLC) and marinobufagenin (MBG), exhibit specificity to α-3 and α-1 Na+,K+-ATPase isoforms, respectively. We compared regulation of MBG and OLC by acute NaCl loading in Dahl salt-sensitive (DS) and salt-resistant (DR) rats.Methods and Results—An intraperitoneal NaCl load (0.8 g/kg) was given to adult male rats (24 DS and 24 DR). Diuresis, natriuresis, renal excretion, and tissue levels of MBG and OLC were measured. Inhibition of renal Na+,K+-ATPase by MBG and ouabain was compared in DS, DR, and Wistar rats. DS (versus DR) exhibited a smaller peak (2 hours) natriuretic response (1.34±0.10 versus 2.08±0.14 mmol · kg−1· h−1;P<0.01), despite a greater plasma Na+(153±2 versus 145±1 mmol/L;P<0.01). In DS and DR, pituitary, adrenal, and plasma OLC exhibited transient 2-fold to 3-fold increases, followed by a decrease to baseline levels. Plasma and adrenal MBG doubled in both strains within 1 hour of NaCl loading and remained elevated. Eight-hour MBG excretion in DS was 4-fold greater than in DR (15.8±0.8 versus 3.6±0.4 pmol;P<0.01), whereas OLC excretion in DS was only 30% greater than in DR (16.1±1.1 and 11.9±0.8 pmol;P<0.05). Kidney Na+,K+-ATPase (α-1 isoform) from Wistar rats and DS exhibited greater sensitivity to MBG than to ouabain.Conclusions—NaCl loading of DS causes transient increase in OLC but sustained increases in MBG tissue levels and excretion. We hypothesize that increased MBG production occurs in an attempt to compensate for genetically impaired pressure-natriuresis mechanisms.