Cardiometabolic effects of DOCA-salt in male C57BL/6J mice are variably dependent on sodium and nonsodium components of diet. Am J Physiol Regul Integr Comp Physiol 2022 Jun 01;322(6):R467-R485
Date
03/30/2022Pubmed ID
35348007Pubmed Central ID
PMC9054347DOI
10.1152/ajpregu.00017.2022Scopus ID
2-s2.0-85129779185 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
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 5L0D (0.39% Na), Envigo 7913 (0.31% Na), Envigo 2920x (0.15% 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 × treatment interaction that impacts the use and interpretation of a common rodent model of low-renin hypertension.
Author List
Patil CN, Ritter ML, Wackman KK, Oliveira V, Balapattabi K, Grobe CC, Brozoski DT, Reho JJ, Nakagawa P, Mouradian GC Jr, Kriegel AJ, Kwitek AE, Hodges MR, Segar JL, Sigmund CD, Grobe JLAuthors
Justin L. Grobe PhD Professor in the Physiology department at Medical College of WisconsinMatthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin
Alison J. Kriegel PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin
Gary C. Mouradian PhD Assistant Professor in the Physiology department at Medical College of Wisconsin
Pablo Nakagawa PhD Assistant Professor in the Physiology department at Medical College of Wisconsin
Chetan N. Patil Research Scientist I in the Pediatrics department at Medical College of Wisconsin
John J. Reho Research Scientist II in the Physiology department at Medical College of Wisconsin
Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAquaporin 2
Blood Pressure
Desoxycorticosterone
Desoxycorticosterone Acetate
Diet
Hypertension
Male
Mice
Mice, Inbred C57BL
Renin
Sodium
