Endogenous cardiotonic steroids and differential patterns of sodium pump inhibition in NaCl-loaded salt-sensitive and normotensive rats.
BACKGROUND
Endogenous sodium pump inhibitors promote sodium excretion in normotensives and contribute to vasoconstriction in NaCl-sensitive hypertension. Marinobufagenin (MBG), an endogenous bufadienolide inhibitor of alpha-1 sodium pump, contributes to hypertension in Dahl salt-sensitive rats (DS). We hypothesized that in NaCl-loaded DS and normotensive Sprague-Dawley rats (S-D), MBG would elicit different patterns of sodium pump inhibition.


METHODS
We compared systolic blood pressure (SBP), renal sodium excretion, activity of the sodium pump in aorta and renal medulla, and levels of MBG, atrial natriuretic peptide (ANP), and cyclic guanosine monophosphate (cGMP) in salt-loaded DS and S-D (20% NaCl, 2.5 ml/kg, intraperitoneally).


RESULTS
NaCl loading produced sustained elevations in renal MBG excretion in both DS (2.41 +/- 0.24 vs. 0.79 +/- 0.08 pmol/h/kg, P < 0.01) and S-D (1.97 +/- 0.37 vs. 0.60 +/- 0.07 pmol/h/kg, P < 0.01) vs. that at baseline (n = 10 for each group). In NaCl-loaded DS, SBP rose by 18 mm Hg (P < 0.01) and aortic sodium pump was inhibited by 22% (P < 0.05 vs. control), while in S-D, SBP and activity of aortic sodium pump did not change. NaCl-loaded S-D excreted twice as much sodium as DS; in S-D, renal sodium pump was inhibited by 24% vs. 14% inhibition in DS (P < 0.05). NaCl loading elicited increases in plasma ANP and in renal cGMP excretion in S-D but not in DS.


CONCLUSIONS
Our present observations demonstrate that in NaCl-loaded S-D and DS, a comparable MBG response is associated with preferential inhibition of the sodium pump in the kidney and in vascular smooth muscle, respectively, resulting in an adaptive natriuresis in S-D but sodium retention and pressor response in DS.
Bagrov
Alexei Y
AY
Laboratory of Cardiovascular Science, National Institute of Aging, NIH, Baltimore, Maryland, USA.
Agalakova
Natalia I
NI
Kashkin
Vladimir A
VA
Fedorova
Olga V
OV
D000818:Animals; D002018:Bufanolides / Q000378:metabolism* / Q000494:pharmacology; D002301:Cardiac Glycosides / Q000378:metabolism* / Q000494:pharmacology; D006152:Cyclic GMP / Q000652:urine; D007668:Kidney / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D020303:Rats, Inbred Dahl; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D002018:Bufanolides; D002301:Cardiac Glycosides; D017673:Sodium Chloride, Dietary; C093896:marinobufagenin; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP