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Angiotensinergic signaling in the brain mediates metabolic effects of deoxycorticosterone (DOCA)-salt in C57 mice. Hypertension 2011 Mar;57(3):600-7

Date

01/26/2011

Pubmed ID

21263123

Pubmed Central ID

PMC3144490

DOI

10.1161/HYPERTENSIONAHA.110.165829

Scopus ID

2-s2.0-79953191408 (requires institutional sign-in at Scopus site)   78 Citations

Abstract

Low-renin hypertension accounts for ≈ 25% of essential hypertensive patients. It is modeled in animals by chronic delivery of deoxycorticosterone acetate and excess dietary sodium (the DOCA-salt model). Previous studies have demonstrated that DOCA-salt hypertension is mediated through activation of the brain renin-angiotensin system. Here, we demonstrate robust metabolic phenotypes of DOCA-salt treatment. Male C57BL/6J mice (6 to 8 weeks old) received a subcutaneous pellet of DOCA (50 mg for 21 days) and were offered a 0.15 mol/L NaCl drink solution in addition to regular chow and tap water. Treatment resulted in mild hypertension, a blunting of weight gain, gross polydipsia, polyuria, and sodium intake, alterations in urinary sodium and potassium turnover, and serum sodium retention. Most strikingly, DOCA-salt mice exhibited no difference in food intake but did exhibited a large elevation in basal metabolic rate. Normalization of blood pressure by hydralazine (500 mg/L in drink solutions) attenuated the hydromineral phenotypes and renal renin suppression effects of DOCA-salt but had no effect on the elevated metabolic rate. In contrast, intracerebroventricular infusion of the angiotensin II type 1 receptor antagonist losartan (5 μg/h) attenuated the elevation in metabolic rate with DOCA-salt treatment. Together, these data illustrate the necessity of angiotensinergic signaling within the brain, independent of blood pressure alterations, in the metabolic consequences of DOCA-salt treatment.

Author List

Grobe JL, Buehrer BA, Hilzendeger AM, Liu X, Davis DR, Xu D, Sigmund CD

Authors

Justin L. Grobe PhD Professor in the Physiology 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

Analysis of Variance
Angiotensins
Animals
Basal Metabolism
Blood Pressure
Brain
Calorimetry
Desoxycorticosterone
Eating
Hypertension
Male
Mice
Mice, Inbred C57BL
Renin
Renin-Angiotensin System
Signal Transduction
Sodium, Dietary
Statistics, Nonparametric