Ov. Fedorova et al., Endogenous Na,K pump ligands are differentially regulated during acute NaCl loading of Dahl rats, CIRCULATION, 102(24), 2000, pp. 3009-3014
Citations number
28
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background-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 (D
R) rats.
Methods and Results-An intraperitoneal NaCl load (0.8 g/kg) was given to ad
ult male rats (24 DS and 24 DR). Diuresis, natriuresis, renal excretion, an
d tissue levels of MBG and OLC were measured. Inhibition of renal Na+,K+-AT
Pase by MBC 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 v
ersus 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 strai
ns within 1 hour of NaCl loading and remained elevated. Eight-hour MBG excr
etion 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 isofor
m) from Wistar rats and DS exhibited greater sensitivity to MBC than to oua
bain.
Conclusions-NaCl loading of DS causes transient increase in OLC but sustain
ed increases in MBG tissue levels and excretion. We hypothesize that increa
sed MBG production occurs in an attempt to compensate for genetically impai
red pressure-natriuresis mechanisms.