Plasma level of the endogenous sodium pump ligand marinobufagenin is related to the salt-sensitivity in men

OBJECTIVE:: Salt-induced elevation of the endogenous digitalis like sodium pump ligand marinobufagenin (MBG) in the Dahl salt-sensitive rats resulted in elevated blood pressure (BP). Here, we tested, in humans, whether MBG levels are related to ambulatory 24-h BP (ABP), controlled long-term increase of salt-intake induces changes in MBG and any salt-induced change in MBG is related to salt sensitivity. METHODS:: Thirty-nine healthy individuals (53±11 years old; 20 men and 19 women) had a total daily NaCl intake of 50mmol (low-salt) and 150mmol (high-salt) for 4 weeks each, in a random order. ABP and MBG in plasma and urine were measured at baseline (unstandardized salt intake) and after high and low-salt intake. RESULTS:: At baseline, plasma MBG (P-MBG) was related to 24-h SBP (r=0.43, P=0.007) and DBP (r=0.32, P=0.047), whereas 24-h urinary excretion of MBG (UE-MBG) was related to 24-h DBP only (r=0.42, P=0.008). Sex-specific analyses revealed that these relationships were significant in men only. Compared with low-salt, high-salt diet increased P-MBG (P=0.029), mainly driven by results in men. Male P-MBG responders vs. nonresponders (above vs. below median of high-salt induced P-MBG increase) had markedly enhanced SBP (10.4±6.4 vs. 1.0±6.0mmHg; P=0.003) and DBP (6.7±5.0 vs. -0.6±3.6mmHg; P=0.001) salt sensitivity. CONCLUSION:: In men, MBG increases with 24-h ABP, and similar to Dahl salt-sensitive rats, 4 weeks of high-salt induced MBG response is accompanied by marked salt sensitivity. However, these patterns seem to be sex-specific and are not observed in women.