期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 322, 期 6, 页码 R467-R485出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00017.2022
关键词
deoxycorticosterone; diet; fluid; hypertension; metabolism
类别
资金
- MCW Biomedical Resource Center
- MCW Comprehensive Rodent Metabolic Phenotyping Core
- National Institutes of Health [HL134850, HL084207, HL007852, HL144807, HL153101, HL122358, ES005605]
- American Heart Association [18EIA33890055, 20CDA3510121, 903246, 898067]
- Children's Research Institute [CRI22700]
- American Physiological Society Postdoctoral Fellowship program
- Advancing a Healthier Wisconsin Endowment
- MCW Clinical and Translational Science Institute [UL1TR001436]
This study investigates the interaction between environmental factors such as diet composition and sodium content and phenotype development in the DOCA-salt model. The results show that there is an interaction between diet and DOCA-salt treatment, affecting energy balance, fluid and electrolyte homeostasis, renal functions, and blood pressure. Interestingly, some phenotypes such as blood pressure and hydration are also dependent on nonsodium dietary components.
Hypertension characterized by low circulating renin activity accounts for roughly 25%-30% of primary hypertension in humans and can be modeled experimentally via deoxycorticosterone acetate (DOCA)-salt treatment. In this model, phenotypes develop in progressive phases, although the timelines and relative contributions of various mechanisms to phenotype development can be distinct between laboratories. To explore interactions among environmental influences such as diet formulation and dietary sodium (Na) content on phenotype development in the DOCA-salt paradigm, we examined an array of cardiometabolic endpoints in young adult male C57BL/6J mice during sham or DOCA-salt treatments when mice were maintained on several common, commercially available laboratory rodent chow diets including PicoLab 5LOD (0.39% Na), Envigo 7913 (0.31% Na), Envigo 2920x (015% Na), or a customized version of Envigo 2920x (0.4% Na). Energy balance (weight gain, food intake, digestive efficiency, and energy efficiency), fluid and electrolyte homeostasis (fluid intake, Na intake, fecal Na content, hydration, and fluid compartmentalization), renal functions (urine production rate, glomerular filtration rate, urine Na excretion, renal expression of renin, vasopressin receptors, aquaporin-2 and relationships among markers of vasopressin release, aquaporin-2 shedding, and urine osmolality), and blood pressure, all exhibited changes that were subject to interactions between diet and DOCA-salt. Interestingly, some of these phenotypes, including blood pressure and hydration, were dependent on nonsodium dietary components, as Na-matched diets resulted in distinct phenotype development. These findings provide a broad and robust illustration of an environment x treatment interaction that impacts the use and interpretation of a common rodent model of low-renin hypertension.
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