Angiotensinergic signaling in the brain mediates metabolic effects of deoxycorticosterone (DOCA)-salt in C57 mice.
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.
Department of Pharmacology, Roy J and Lucille A. Carver College of Medicine, University of Iowa, 3181 MERF, 375 Newton Rd, Iowa City, IA 52242, USA. justin-grobe@uiowa.edu
Justin L
JL
Grobe
Beth A
BA
Buehrer
Aline M
AM
Hilzendeger
Xuebo
X
Liu
Deborah R
DR
Davis
Di
D
Xu
Curt D
CD
Sigmund
D000704:Analysis of Variance; D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D001481:Basal Metabolism / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002151:Calorimetry; D003900:Desoxycorticosterone / Q000378:metabolism / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000378:metabolism; D018709:Statistics, Nonparametric
D000809:Angiotensins; D012982:Sodium, Dietary; D003900:Desoxycorticosterone; D012083:Renin
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