High-Salt Diet Augments Systolic Blood Pressure and Induces Arterial Dysfunction in Outbred, Genetically Diverse Mice
Authors: Zheng Xiangyu , Berg Sen Jennifer , Li Zhuoxin , Sabouri Mostafa , Samarah Luaye , Deacon Christina , Bernardo Joseph , Machin Daniel 
Published: May 2023

One of the most important lifestyle factors that contributes to cardiovascular disease risk is excess dietary salt intake. In the US, ~90% of adults consume too much salt, and the average salt intake is ~2.3x higher than recommended by the American Heart Association. Excess salt consumption contributes to cardiovascular disease risk by elevating systolic blood pressure (BP) and inducing arterial dysfunction in humans. However, this arterial phenotype is not typically observed in inbred, genetically identical mouse strains that consume a high-salt (HS) diet, which may be due to strain-specific resistance to HS diet. Thus, we sought to determine the effects of HS diet consumption on systolic BP and arterial function in UM-HET3 mice, an outbred, genetically diverse strain of mice. Male and female UM-HET3 mice underwent a low-salt (1% NaCl [LS]) or HS (4% NaCl) diet for 12 weeks. Systolic BP was increased after 2 weeks and aortic stiffness, determined by pulse wave velocity (PWV), was increased after 4 weeks in HS mice compared to baseline (P<0.05). Systolic BP and PWV continued to increase throughout the 12-week dietary intervention in HS mice (P<0.05), while systolic BP and PWV were unchanged in LS mice over the same timeframe (P>0.05). Histological analysis revealed that aortic collagen content was ~81% higher in HS compared to LS mice (P<0.05). Aortic elastin content, lumen diameter, medial wall-to-lumen ratio, and medial cross-sectional area were similar between groups (P>0.05). Endothelium‑dependent dilation (EDD), determine by carotid artery vasodilation to acetylcholine (ACh), was ~10% lower in HS compared to LS mice (P<0.05). In the presence of the nitric oxide (NO) synthase inhibitor, L-NAME, ACh-mediated dilation was blunted in HS and LS mice (P<0.05 vs ACh), but was similar between groups (P>0.05). There was a tendency for NO-mediated vasodilation, determined by subtracting ACh+L-NAME max vasodilation from ACh max vasodilation, to be higher in LS compared to HS mice (P=0.057). Endothelium-independent dilation (EID), determined by carotid artery vasodilation to sodium nitroprusside, was similar between groups (P>0.05). Lastly, there was a strong relationship between systolic BP and PWV (r2=0.40, P<0.05), as well as inverse relationships between EDD and systolic BP (r2=0.21, P<0.05) or PWV (r2=0.20, P<0.05). However, no relationship between systolic BP or aortic stiffness and EID was present (P>0.05). Lastly, we observed no sex-related difference in any measurement of arterial function (P>0.05 for all). Taken together, these findings provide evidence that a HS diet in UM-HET3 mice induces progressive elevations in systolic BP and aortic stiffness, which are accompanied by impaired EDD. These data suggest that outbred, genetically diverse mice may provide unique translational insight into HS diet-induced elevations in systolic BP and arterial dysfunction in humans living in industrialized societies.

This study was funded in part by a grant from the National Institutes of Health (R00 AT010017).

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.