Angiotensin II‐Induced Increase in Blood Pressure in Mice Consuming High Salt and High Fructose Diet: Females Not Protected

Abstract

Hypertension presents major risk factors for cardiovascular and renal disease. High salt and high fructose (HSHF) consumption contribute to hypertension via salt retention and obesity. Sex differences in blood pressure regulation are well known. Some studies have shown protection for females from angiotensin II (AngII)‐induced and dietary‐induced increase in blood pressure. Our results indicate that HSHF consumption increases blood pressure in male and female mice. Also, AngII administration increased blood pressure in male and female mice while consuming normal diet with water, but no sex differences were noted (Rouch, A. FASEB J. 32(1) A904.6, 2018). The objective of this study was to determine the effects of AngII on blood pressure, sodium excretion, and urine flow rate in male and female CD‐1 mice while consuming a HSHF diet. Four groups of mice included male‐vehicle, male‐AngII, female‐vehicle, and female‐AngII (n=6/group). Mice at four weeks of age were placed in metabolic cages for a 5‐day baseline period followed by a ten‐day AngII period where AngII was administered via an Alzet® osmotic minipump containing either saline (vehicle) or AngII to yield 1mg/kg/min. All mice consumed a diet of 4% salt with fluid containing 1% NaCl and 20% fructose ad libitum. Systolic blood pressure was measured daily via the tail‐cuff method (CODA, Kent Scientific). Excessive fluid retention evidenced by a significant increase in body weight of 4–5 g occurred in the AngII‐treated mice of both sexes in the first 5 days of the AngII period. One mouse of each AngII‐treated group died before the end of the AngII period while the other mice recovered to their normal body weight by the end of the ten‐day period. AngII increased systolic blood pressure (mmHg) in females from 108.0 ± 3.4 to 130.0 ± 6.1 (p<0.0001) and in males from 101.1 ± 1.3 to 127.5 ± 3.2 (p<0.0001). In both AngII‐treated groups, daily urine flow rate and sodium excretion demonstrated biphasic patterns of significant decreases in the first 5 days of the AngII period followed by increased levels to achieve fluid and sodium balance. We conclude that AngII‐infusion during HSHF consumption in mice presents with potentially fatal salt and water retention. No sex differences in the AngII‐induced increase in SBP or renal handling of sodium were measured. Support or Funding Information OK‐INBRE SURP