Introduction: Metabolic syndrome (MetS) enhances salt sensitivity of blood pressure and is responsible for cardiovascular disease. However, few studies have reported the effects of dietary salt restriction on the link between cardiovascular and metabolic disorders in MetS. We investigated whether dietary salt restriction might ameliorate cardiac and adipose tissue injury in a rat model of MetS.
Methods and Results: We used DahlS.Z-Leprfa/Leprfa (DS/obese) rats which are derived from a cross between Dahl salt-sensitive and Zucker rats and represent a new animal model of MetS. DS/obese rats were fed a normal-salt (0.36% NaCl in chow) or low-salt (0.0466% NaCl in chow) diet from 9 weeks of age and were compared with homozygous lean littermates (DahlS.Z-Lepr+/Lepr+, or DS/lean rats). DS/obese rats fed the normal-salt diet progressively developed severe hypertension and showed left ventricular (LV) hypertrophy, fibrosis, and LV diastolic dysfunction at 15 weeks of age. Dietary salt restriction markedly attenuated all of these changes in DS/obese rats. The levels of cardiac oxidative stress and inflammation and the expression of cardiac renin-angiotensin-aldosterone system genes were increased in DS/obese rats fed the normal-salt diet, and these parameters were down-regulated by dietary salt restriction in both DS/obese and DS/lean rats. In addition, dietary salt restriction suppressed the increases in visceral adipose tissue inflammation and circulating proinflammatory cytokines apparent in DS/obese rats. Body weight and visceral adipocyte size were not affected by dietary salt restriction. Dietary salt restriction did not alter fasting serum glucose levels, but it markedly reduced the fasting serum insulin concentration and the HOMA-IR in DS/obese rats.
Conclusions: Dietary salt restriction not only prevents hypertension and cardiac injury but also ameliorates systemic and adipose tissue inflammation and insulin resistance, without affecting obesity, in this model of MetS.