We studied the effect of dietary NaCl restriction performed in middle-aged/older adults (8 men and 3 women;60+/-2 yrs) with moderately elevated systolic BP (SBP: 139+/-2;DBP: 83+/-2 mmHg). We measured urinary and plasma MBG levels, SBP, aPWV (randomized, placebo-controlled, cross-over design). We also explored the associations of MBG excretion with SBP and aPWV across conditions of 5 weeks of a low NaCl (LS;77+/-9 mmol/day) and 5 weeks of a normal NaCl (NS;144+/-7 mmol/day) diet. Markers of oxidative stress were also assessed. SBP (127+/-3 mmHg vs. 138+/- 5 mmHg;P<0.05) and aPWV (700+/-40 cm/sec vs. 843 +/- 36 cm/sec, 17% of reduction, P<0.05) were reduced following a 5-week low sodium vs. 5-week normal sodium diet (randomized, cross-over design). Urinary MBG excretion (weekly measurements) was lower during the LS vs. NS condition (25.4+/-1.8 vs. 30.7+/-2.1 pmol/kg/day, p<0.05) and was positively correlated with SBP (r=0.39, p<0.001) and sodium excretion (r = 0.46, p<0.001) across the 10 weeks. These relations persisted during the NS but not the LS condition (p<0.005). MBG excretion also was positively related to aPWV (r=0.51, p<0.05) and endothelial cell expression of the oxidant enzyme NAD(P)H oxidase-p47phox (r=0.53, p<0.05). In summary, the present results demonstrate that dietary sodium restriction reduces renal MBG excretion in middle-aged and older adults with moderately elevated systolic blood pressure. Our findings suggest that this reduction in MBG may contribute, possibly via reduced oxidative stress, to the reductions in large elastic artery stiffness and SBP that accompanied dietary sodium reduction. Given age-associated increases in arterial stiffness, SBP and salt sensitivity, these results echo recent calls for reduced sodium intake in the American diet, particularly in the rapidly growing, at-risk population of middle-aged and older adults. These results show, for the first time in humans, that dietary salt restriction reduces MBG excretion, and this is associated with reductions in SBP and aPWV, and with improved elasticity of blood vessels. In addition, MBG is positively related to SBP during sodium intake typical of an American diet, complimenting existing evidence in rodents/humans fed experimentally high sodium diets.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000609-21
Application #
8736576
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
21
Fiscal Year
2013
Total Cost
$438,030
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Fedorova, Olga V; Emelianov, Igor V; Bagrov, Konstantin A et al. (2015) Marinobufagenin-induced vascular fibrosis is a likely target for mineralocorticoid antagonists. J Hypertens 33:1602-10
Grigorova, Yulia N; Juhasz, Ondrej; Zernetkina, Valentina et al. (2015) Aortic Fibrosis, Induced by High Salt Intake in the Absence of Hypertensive Response, Is Reduced by a Monoclonal Antibody to Marinobufagenin. Am J Hypertens :
Fedorova, Olga V; Zernetkina, Valentina I; Shilova, Victoria Y et al. (2015) Synthesis of an Endogenous Steroidal Na Pump Inhibitor Marinobufagenin, Implicated in Human Cardiovascular Diseases, Is Initiated by CYP27A1 via Bile Acid Pathway. Circ Cardiovasc Genet 8:736-45
Fedorova, Olga V; Lakatta, Edward G; Bagrov, Alexei Y et al. (2015) Plasma level of the endogenous sodium pump ligand marinobufagenin is related to the salt-sensitivity in men. J Hypertens 33:534-41; discussion 541
Kennedy, David J; Shrestha, Kevin; Sheehey, Brendan et al. (2015) Elevated Plasma Marinobufagenin, An Endogenous Cardiotonic Steroid, Is Associated With Right Ventricular Dysfunction and Nitrative Stress in Heart Failure. Circ Heart Fail 8:1068-76
Jablonski, Kristen L; Fedorova, Olga V; Racine, Matthew L et al. (2013) Dietary sodium restriction and association with urinary marinobufagenin, blood pressure, and aortic stiffness. Clin J Am Soc Nephrol 8:1952-9
Zazerskaya, Irina E; Ishkaraeva, Valentina V; Frolova, Elena V et al. (2013) Magnesium Sulfate Potentiates Effect of Digifab on Marinobufagenin-Induced Na/K-ATPase Inhibition. Am J Hypertens :
Piecha, Grzegorz; Koleganova, Nadezda; Ritz, Eberhard et al. (2012) High salt intake causes adverse fetal programming--vascular effects beyond blood pressure. Nephrol Dial Transplant 27:3464-76
Kolmakova, Elena V; Haller, Steven T; Kennedy, David J et al. (2011) Endogenous cardiotonic steroids in chronic renal failure. Nephrol Dial Transplant 26:2912-9
Fedorova, Olga V; Shapiro, Joseph I; Bagrov, Alexei Y (2010) Endogenous cardiotonic steroids and salt-sensitive hypertension. Biochim Biophys Acta 1802:1230-6

Showing the most recent 10 out of 15 publications