Angiotensinergic signaling in the brain mediates metabolic effects of deoxycorticosterone (DOCA)-salt in C57 mice

JL Grobe, BA Buehrer, AM Hilzendeger, X Liu… - …, 2011 - Am Heart Assoc
JL Grobe, BA Buehrer, AM Hilzendeger, X Liu, DR Davis, D Xu, CD Sigmund
Hypertension, 2011Am Heart Assoc
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 …
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.
Am Heart Assoc