Endogenous Na,K pump ligands are differentially regulated during acute NaCl loading of Dahl rats.
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 (DR) rats.


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 (alpha-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.
Fedorova
O V
OV
Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, Baltimore, MD 21224, USA.
Lakatta
E G
EG
Bagrov
A Y
AY
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002018:Bufanolides / Q000378:metabolism*; D002298:Cardenolides; D004077:Digoxin; D004573:Electrolytes / Q000097:blood; D004791:Enzyme Inhibitors / Q000378:metabolism; D016623:Ion Pumps / Q000378:metabolism*; D008297:Male; D010042:Ouabain / Q000737:chemistry / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D020303:Rats, Inbred Dahl; D012503:Saponins / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D002018:Bufanolides; D002298:Cardenolides; D004573:Electrolytes; D004791:Enzyme Inhibitors; D016623:Ion Pumps; D012503:Saponins; C034504:digoxin-like factors; C093896:marinobufagenin; D012965:Sodium Chloride; D010042:Ouabain; D004077:Digoxin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium