Olga V Fedorova1, Edward G Lakatta, Alexei Y Bagrov, Olle Melander. 1. aLaboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA bDepartment of Clinical Sciences, Lund University cDepartment of Internal Medicine, Skåne University Hospital, Malmö, Sweden.
Abstract
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 50 mmol (low-salt) and 150 mmol (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 ± 6.0 mmHg; P = 0.003) and DBP (6.7 ± 5.0 vs. -0.6 ± 3.6 mmHg; 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.
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 50 mmol (low-salt) and 150 mmol (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 ± 6.0 mmHg; P = 0.003) and DBP (6.7 ± 5.0 vs. -0.6 ± 3.6 mmHg; 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.
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