High fructose diet activates plasma ACE and renal ACE2

Abstract

Dietary fructose in mice increases blood pressure via activation of the renin angiotensin system. To extend these findings, we tested the effect of an angiotensin AT1 antagonist, losartan, on cardiovascular parameters and ACE/ACE2 activity. Male C57BL mice were fed a 60% fructose diet for 10 weeks. Telemetric probes were implanted at week 8 and losartan (30 mg/kg/day) was given in the drinking water during the last week. Desorption/Ionization Mass Spectrometry (SELDI‐TOF‐MS) and fluorigenic assays were used to evaluate plasma ACE and kidney ACE2 activity, respectively. The SELDI‐TOF‐MS proteolytic assays use endogenous Ang substrates; Ang I for ACE and Ang II for ACE2. Losartan reduced MAP by 16% (117±1 to 99±3 mmHg) in the fructose group, while it had no effect in controls. There were no alterations in HR. Plasma Ang II and ACE activity were higher in the fructose group (Ang II: 12±3 vs. 37±8 pg/ml; ACE: 1.12±0.64 vs. 4.67±1.3; AngII/Ang I). There was no alteration in kidney ACE activity between groups. Kidney ACE2 activity was increased in fructose group (2.83±0.231 vs. 3.94±0.119 pmol/hr/μg protein; control vs fructose). Fructose consumption enhanced the BP lowering effect of losartan. Increased renal ACE2 activity could play a renoprotective role and/or could be a feedback response to counteract the increased BP and plasma ACE activity observed in fructose fed mice.