Dietary sodium restriction and association with urinary marinobufagenin, blood pressure, and aortic stiffness.
OBJECTIVE
Systolic BP and large elastic artery stiffness both increase with age and are reduced by dietary sodium restriction. Production of the natriuretic hormone marinobufagenin, an endogenous α1 Na+,K+-ATPase inhibitor, is increased in salt-sensitive hypertension and contributes to the rise in systolic BP during sodium loading.


METHODS
The hypothesis was that dietary sodium restriction performed in middle-aged/older adults (eight men and three women; 60 ± 2 years) with moderately elevated systolic BP (139 ± 2/83 ± 2 mmHg) would reduce urinary marinobufagenin excretion as well as systolic BP and aortic pulse-wave velocity (randomized, placebo-controlled, and crossover design). This study also explored the associations among marinobufagenin excretion with systolic BP and aortic pulse-wave velocity across conditions of 5 weeks of a low-sodium (77 ± 9 mmol/d) and 5 weeks of a normal-sodium (144 ± 7 mmol/d) diet.


RESULTS
Urinary marinobufagenin excretion (weekly measurements; 25.4 ± 1.8 versus 30.7 ± 2.1 pmol/kg per day), systolic BP (127 ± 3 versus 138 ± 5 mmHg), and aortic pulse-wave velocity (700 ± 40 versus 843 ± 36 cm/s) were lower during the low- versus normal-sodium condition (all P<0.05). Across all weeks, marinobufagenin excretion was related with systolic BP (slope=0.61, P<0.001) and sodium excretion (slope=0.46, P<0.001). These associations persisted during the normal- but not the low-sodium condition (both P<0.005). Marinobufagenin excretion also was associated with aortic pulse-wave velocity (slope=0.70, P=0.02) and endothelial cell expression of NAD(P)H oxidase-p47phox (slope=0.64, P=0.006).


CONCLUSIONS
These results show, for the first time in humans, that dietary sodium restriction reduces urinary marinobufagenin excretion and that urinary marinobufagenin excretion is positively associated with systolic BP, aortic stiffness (aortic pulse-wave velocity), and endothelial cell expression of the oxidant enzyme NAD(P)H oxidase. Importantly, marinobufagenin excretion is positively related to systolic BP over ranges of sodium intake typical of an American diet, extending previous observations in rodents and humans fed experimentally high-sodium diets.
Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado;, †Intramural Research Program, Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland;, ‡Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, United Kingdom, §Division of Renal Diseases and Hypertension, University of Colorado Denver Anschutz Medical Center, Aurora, Colorado.
Kristen L
KL
Jablonski
Olga V
OV
Fedorova
Matthew L
ML
Racine
Candace J
CJ
Geolfos
Phillip E
PE
Gates
Michel
M
Chonchol
Bradley S
BS
Fleenor
Edward G
EG
Lakatta
Alexei Y
AY
Bagrov
Douglas R
DR
Seals
D000368:Aged; D015415:Biomarkers / Q000652:urine; D001794:Blood Pressure; D002018:Bufanolides / Q000652:urine*; D003120:Colorado; D018592:Cross-Over Studies; D004039:Diet, Sodium-Restricted; D004311:Double-Blind Method; D042783:Endothelial Cells / Q000201:enzymology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000178:diet therapy* / Q000503:physiopathology / Q000652:urine; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D063177:Pulse Wave Analysis; D013997:Time Factors; D016896:Treatment Outcome; D059289:Vascular Stiffness
D015415:Biomarkers; D002018:Bufanolides; C093896:marinobufagenin; D019255:NADPH Oxidases