Abstract P239: Diet Modifies Cardiometabolic Effects Of DOCA-salt In C57BL/6J Mice

Abstract

The deoxycorticosterone acetate (DOCA)-salt model of hypertension is widely used to investigate the neurohormonal regulation of blood pressure. We investigated the modulatory effect of three common “chow” diets upon cardiometabolic consequences of DOCA-salt treatment in mice. Male C57BL/6J mice (6 wks of age) were randomly assigned to 5L0D (LabDiet 67138, 4.0 g Na/kg), a Soy-free extruded diet (Envigo 2920, 1.5 g Na/kg), or an NIH-31 modified open formula diet (Teklad 7913, 3.1 g Na/kg) and provided with autoclaved deionized water for 3 weeks (n=16/diet). At 9 weeks of age (ie, before DOCA-salt), intake behaviors and energy flux were assessed using metabolic caging and bomb calorimetry. Before DOCA-salt, body mass, digestive efficiency, energy efficiency, total sodium intake, urine volumes, and apparent sodium & potassium retentions (ie, ingested-urine loss) were significantly modified by diet (p<0.05), but calories absorbed per day was not. Mice (n=8/diet) were then implanted with a DOCA pellet (50mg, sc) and provided 0.15 M NaCl as an additional drink option, or underwent sham surgery (n=8/diet). At 12 weeks of age (ie, after DOCA-salt), intake behaviors and energy flux were again assessed before tissue harvest. After DOCA-salt, body mass, energy efficiency, total sodium intake, urine volume, apparent sodium retention, and renal renin mRNA were significantly affected by a diet x DOCA-salt interaction (p<0.05). In contrast, digestive efficiency and apparent potassium retention were modified by diet (p<0.05), and calories absorbed per day, plasma sodium, and plasma potassium were affected by main effects of diet (p<0.05) and DOCA-salt (p<0.05), but these endpoints were not modified by a diet x DOCA-salt interaction. Combined with analyses of tissue masses, expression of various renal electrolyte transporters, blood chemistries, and urinalyses, these many endpoints highlight a multitude of cardiometabolic outcomes of the DOCA-salt model that are sensitive to environmental contexts such as diet. Ongoing work is investigating the modulatory effect of diet upon increases in total body sodium retention and blood pressure induced by DOCA-salt treatment, and roles for varied sodium vs protein contents of the diets in these effects.