Impact of casein- versus grain-based diets on rat renal sodium transporters' abundance and regulation

Hypertension-related mortality is on the rise, and evidence ranks hypertension as the top global disease burden and thus, an important public health challenge (1). A component of the hypertension trend can be assigned to lifestyle trends including consumption of higher-sodium/lower-potassium diets, suggesting that reducing these trends could reduce the incidence of hypertension (1⇓⇓–4). For these reasons, definition of molecular mechanisms connecting dietary electrolyte consumption to BP is essential. Preclinical studies varying electrolyte intake in rodents utilize synthetic casein-based chows in which the composition ( e.g ., sodium, potassium, chloride, and bicarbonate) can be well defined. However, in studies not focused on diet, rodents are usually bred, maintained, and studied on grain-based chow. A few studies have noted an effect of chow composition on renal function. For example, maintaining and breeding Dahl salt-sensitive rats on grain chow blunts the offspring’s propensity to develop hypertension and renal injury when fed high-salt casein chow compared with offspring of Dahl rats bred and maintained on casein chow (5), and doubling dietary protein composition of high-salt casein chow exacerbates hypertension, renal damage, and immune infiltration (6). Recent experiments in our group revealed a significant effect of casein chow versus grain chow on the abundance of rat renal sodium transporters (transporters, channels, and claudins) along the nephron both at baseline and in response to the angiotensin II infusion model of hypertension (AngII-HTN). We previously reported that distal Na-Cl cotransporter (NCC) was stimulated during AngII-HTN in …