Dietary Sodium Restriction and Association with Urinary Marinobufagenin, Blood Pressure, and Aortic Stiffness

作者：Jablonski Kristen L^*; Fedorova Olga V; Racine Matthew L; Geolfos Candace J; Gates Phillip E; Chonchol Michel; Fleenor Bradley S; Lakatta Edward G; Bagrov Alexei Y; Seals Douglas R

来源：Clinical Journal of the American Society of Nephrology, 2013, 8(11): 1952-1959.

DOI：10.2215/CJN.00900113

Background and objectivesSystolic 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 1 Na+,K+-ATPase inhibitor, is increased in salt-sensitive hypertension and contributes to the rise in systolic BP during sodium loading.Design, setting, participants, & measurementsThe hypothesis was that dietary sodium restriction performed in middle-aged/older adults (eight men and three women; 602 years) with moderately elevated systolic BP (1392/83 +/- 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.ResultsUrinary 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).ConclusionsThese 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.

• 出版日期2013-11-7