(Circulation. 2000;102:3009.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Endogenous Na,K Pump Ligands Are Differentially Regulated During Acute NaCl Loading of Dahl Rats
Presented in part at the 71st Scientific Sessions of the American Heart Association, Dallas, Tex, November 8–11, 1998, and published in abstract form (Circulation. 1998;98[suppl I]:I-377).
From the Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, Baltimore, Md.
Correspondence to Alexei Y. Bagrov, Laboratory of Cardiovascular Science, National Institute on Aging, 5600 Nathan Shock Dr, Baltimore, MD 21224.
Background—Two mammalian
digitalis-like factors, an ouabain-like compound (OLC) and
marinobufagenin (MBG), exhibit specificity to 
-3 and -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
(-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.
Key Words: hypertension • rats, inbred Dahl • sodium, dietary • Na(+)-K(+)-exchanging ATPase • steroids • bufanolides • ouabain
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