Fedorova O V, Lakatta E G, Bagrov A Y
Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, Baltimore, MD 21224, USA.
Circulation. 2000 Dec 12;102(24):3009-14. doi: 10.1161/01.cir.102.24.3009.
Two mammalian digitalis-like factors, an ouabain-like compound (OLC) and marinobufagenin (MBG), exhibit specificity to alpha-3 and alpha-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.
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 (alpha-1 isoform) from Wistar rats and DS exhibited greater sensitivity to MBG than to ouabain.
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.
两种哺乳动物类洋地黄样因子，一种哇巴因样化合物（OLC）和海蟾蜍精（MBG），分别对α-3和α-1钠钾ATP酶亚型具有特异性。我们比较了急性氯化钠负荷对 Dahl 盐敏感（DS）和盐抵抗（DR）大鼠中 MBG 和 OLC 的调节作用。
给成年雄性大鼠（24 只 DS 和 24 只 DR）腹腔注射氯化钠负荷（0.8 g/kg）。测量利尿、利钠、肾脏排泄以及 MBG 和 OLC 的组织水平。比较了 DS、DR 和 Wistar 大鼠中 MBG 和哇巴因对肾脏钠钾ATP酶的抑制作用。DS（与 DR 相比）的峰值（2 小时）利钠反应较小（1.34±0.10 与 2.08±0.14 mmol·kg⁻¹·h⁻¹；P<0.01），尽管血浆钠水平更高（153±2 与 145±1 mmol/L；P<0.01）。在 DS 和 DR 中，垂体、肾上腺和血浆中的 OLC 呈现短暂的 2 至 3 倍增加，随后降至基线水平。在两种品系中，血浆和肾上腺中的 MBG 在氯化钠负荷后
