Cardiovascular disease remains a major Public Health problem and is the leading cause of death in the US. The degree to which blood pressure (BP) changes in response to a dietary salt manipulation varies widely among humans. Many adults have a minimal change in BP despite large changes in dietary salt, which is termed salt-resistant BP. However, there may be pathophysiological consequences to a high salt diet in humans apart from the effect of salt on BP. Animal models support the conclusion that excess dietary salt contributes to endothelial abnormalities independent of BP. Dietary salt-induced increases in oxidative stress may be one of the factors impairing nitric oxide (NO) release. Based on the foregoing, our global hypothesis is that dietary salt intake will adversely affect vascular endothelial function independently of mean arterial BP in humans. We propose to investigate the effects of dietary salt on endothelial-dependent dilation of a conduit artery (i.e., brachial) and NO-mediated vasodilation of the cutaneous microvessels. We specifically hypothesize that high dietary salt will cause a decline in endothelial-dependent dilation and NO-mediated cutaneous vasodilation. We also hypothesize that oxidative stress will increase during the high dietary salt condition, and that the dietary salt-induced decline in cutaneous vasodilation will be attenuated by local ascorbic acid infusion providing functional evidence for a role of oxidative stress. Endothelial cells will be obtained to assess oxidant damage as well as oxidant and antioxidant enzyme content. These hypotheses will be tested in adults with salt-resistant BP. Young and middle-aged adults will undergo a 21-day controlled feeding study where they will consume a 1.3 g salt diet for 7 days, a 6 g salt diet for 7 days, and a 20 g salt diet for 7 days (crossover design, diet order sequence randomized;fixed potassium intake). Twenty-four hour ambulatory BP and urine collections during each diet condition will permit the individual assessment of salt sensitivity of BP. Flow mediated dilation of the brachial artery will be used to assess conduit endothelial- dependent dilation and cutaneous vasodilation in response to local heating using laser Doppler flowmetry and intradermal microdialysis will be assessed in the forearm to evaluate the microvasculature. Cutaneous vasodilation in response to local heating will be assessed at a Ringers (control) site, L-NAME site (to assess the NO contribution), and an ascorbic acid site (to assess the role of oxidative stress). These measures will be made during the last day of the 1.3g, 6 g, and 20g dietary salt conditions. The range of dietary salt intakes is purposely wide to allow the assessment of dose-response relationships in endothelial responses. This comprehensive endothelial assessment in humans during a controlled feeding study will allow us to determine if excess dietary salt is impairing endothelial-dependent vasodilation at both macro- and microvascular levels.

Public Health Relevance

Dietary salt increases blood pressure in some, but not all adults. There is evidence in experimental animals that excess dietary salt may damage the blood vessels even if blood pressure does not rise. The purpose of this investigation is to determine if this also occurs in middle-aged adults with normal blood pressure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL104106-01A1
Application #
8186146
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Boyington, Josephine
Project Start
2011-09-07
Project End
2015-06-30
Budget Start
2011-09-07
Budget End
2012-06-30
Support Year
1
Fiscal Year
2011
Total Cost
$397,431
Indirect Cost
Name
University of Delaware
Department
Other Health Professions
Type
Schools of Allied Health Profes
DUNS #
059007500
City
Newark
State
DE
Country
United States
Zip Code
19716
Muth, Bryce J; Brian, Michael S; Chirinos, Julio A et al. (2017) Central systolic blood pressure and aortic stiffness response to dietary sodium in young and middle-aged adults. J Am Soc Hypertens 11:627-634
Matthews, Evan L; Brian, Michael S; Edwards, David G et al. (2017) Blood pressure responses to dietary sodium: Association with autonomic cardiovascular function in normotensive adults. Auton Neurosci 208:51-56
Brian, M S; Dalpiaz, A; Matthews, E L et al. (2017) Dietary sodium and nocturnal blood pressure dipping in normotensive men and women. J Hum Hypertens 31:145-150
Farquhar, William B; Edwards, David G; Jurkovitz, Claudine T et al. (2015) Dietary sodium and health: more than just blood pressure. J Am Coll Cardiol 65:1042-50
Matthews, Evan L; Brian, Michael S; Ramick, Meghan G et al. (2015) High dietary sodium reduces brachial artery flow-mediated dilation in humans with salt-sensitive and salt-resistant blood pressure. J Appl Physiol (1985) 118:1510-5
Edwards, David G; Farquhar, William B (2015) Vascular effects of dietary salt. Curr Opin Nephrol Hypertens 24:8-13
DuPont, Jennifer J; Ramick, Meghan G; Farquhar, William B et al. (2014) NADPH oxidase-derived reactive oxygen species contribute to impaired cutaneous microvascular function in chronic kidney disease. Am J Physiol Renal Physiol 306:F1499-506
Lennon-Edwards, Shannon; Allman, Brittany R; Schellhardt, Taylor A et al. (2014) Lower potassium intake is associated with increased wave reflection in young healthy adults. Nutr J 13:39
Lennon-Edwards, S; Ramick, M G; Matthews, E L et al. (2014) Salt loading has a more deleterious effect on flow-mediated dilation in salt-resistant men than women. Nutr Metab Cardiovasc Dis 24:990-5
DuPont, Jennifer J; Greaney, Jody L; Wenner, Megan M et al. (2013) High dietary sodium intake impairs endothelium-dependent dilation in healthy salt-resistant humans. J Hypertens 31:530-6

Showing the most recent 10 out of 11 publications