High-salt diet augments systolic blood pressure and induces arterial dysfunction in outbred, genetically diverse mice.

Excess salt consumption contributes to hypertension and arterial dysfunction in humans living in industrialized societies. However, this arterial phenotype is not typically observed in inbred, genetically identical mouse strains that consume a high-salt (HS) diet. Therefore, we sought to determine the effects of HS diet consumption on systolic blood pressure (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 [LS (1% NaCl)] or HS (4% NaCl) diet for 12 wk. Systolic BP and aortic stiffness, determined by pulse wave velocity (PWV), were increased in HS after 2 and 4 wk, respectively, compared with baseline and continued to increase through week 12 (P < 0.05). Systolic BP was higher from weeks 2-12 and PWV was higher from weeks 4-12 in HS compared with LS mice (P < 0.05). Aortic collagen content was ∼81% higher in HS compared with LS (P < 0.05), whereas aortic elastin content was similar between groups (P > 0.05). Carotid artery endothelium-dependent dilation (EDD) was ∼10% lower in HS compared with LS (P < 0.05), endothelium-independent dilation was similar between groups (P > 0.05). Finally, there was a strong relationship between systolic BP and PWV (r2 = 0.40, P < 0.05), as well as inverse relationship between EDD and systolic BP (r2 = 0.21, P < 0.05) or PWV (r2 = 0.20, P < 0.05). In summary, HS diet consumption in UM-HET3 mice increases systolic BP, which is accompanied by aortic stiffening and impaired EDD. These data suggest that outbred, genetically diverse mice may provide unique translational insight into arterial adaptations of humans that consume an HS diet.NEW & NOTEWORTHY Excess salt consumption is a contributor to hypertension and arterial dysfunction in humans living in industrialized societies, but this phenotype is not observed in inbred, genetically identical mice that consume a high-salt (HS) diet. This study reveals that a HS diet in outbred, genetically diverse mice progressively increases systolic blood pressure and induce arterial dysfunction. These data suggest that genetically diverse mice may provide translational insight into arterial adaptations in humans that consume an HS diet.

Western diet augments metabolic and arterial dysfunction in a sex-specific manner in outbred, genetically diverse mice.

Western diet (WD), characterized by excess saturated fat and sugar intake, is a major contributor to obesity and metabolic and arterial dysfunction in humans. However, these phenotypes are not consistently observed in traditional inbred, genetically identical mice. Therefore, we sought to determine the effects of WD on visceral adiposity and metabolic/arterial function in UM-HET3 mice, an outbred, genetically diverse strain of mice. Male and female UM-HET3 mice underwent normal chow (NC) or WD for 12 weeks. Body mass and visceral adiposity were higher in WD compared to NC (P < 0.05). Female WD mice had greater visceral adiposity than male WD mice (P < 0.05). The results of glucose and insulin tolerance tests demonstrated that metabolic function was lower in WD compared to NC mice (P < 0.05). Metabolic dysfunction in WD as was driven by male mice, as metabolic function in female WD mice was unchanged (P > 0.05). Systolic blood pressure (BP) and aortic stiffness were increased in WD after 2 weeks compared to baseline and continued to increase through week 12 (P < 0.05). Systolic BP and aortic stiffness were higher from weeks 2-12 in WD compared to NC (P < 0.05). Aortic collagen content was higher in WD compared to NC (P < 0.05). Carotid artery endothelium-dependent dilation was lower in WD compared to NC (P < 0.05). These data suggest sex-related differences in visceral adiposity and metabolic dysfunction in response to WD. Despite this, arterial dysfunction was similar in male and female WD mice, indicating this model may provide unique translational insight into similar sex-related observations in humans that consume WD.