Fructose/losartan interactions: Effects on renal ACE2

Abstract

Fructose diet enhances losartan's hypotensive effect in mice. Angiotensin‐converting enzyme 2 (ACE2) has emerged as an important component of the renin angiotensin system. We examined the interactions between fructose diet and losartan on renal ACE/ACE2 balance. Male C57BL mice were fed a 60% fructose diet for 10 weeks and losartan (Los, 30mg/kg/day) was given in the drinking water for the last wk. Renal ACE and ACE2 activity were measured by radiofluorescent and fluorogenic assays, respectively. Renal Ang II levels were measured by RIA. Renal ACE and ACE2 protein expression were measured by Western blots. There was no alteration in renal ACE activity or protein expression between groups. Renal Ang II, ACE2 activity and ACE2 protein expression were increased in fructose group (Ang II: 112 ± 40 vs. 440 ± 114 pg/μg protein; ACE2 activity: 2.8 ± 0.2 vs. 3.9 ± 0.2 pmol/hr/ ?g protein; ACE2 protein expression: 0.6 ± 0.1 vs. 1.3 ± 0.1 AU). Los had no effect on renal Ang II or ACE protein or activity. Los increased ACE2 protein in controls (0.7 ± 0.1 vs. 1.4 ± 0.2, AU) with no change in activity. In fructose mice, Los decreased renal Ang II (440 ± 114 vs. 190 ± 85 pg/µg protein). Fructose produced consistent activation of the renal ACE2 system while Los produced no additional effects. Results suggest that interaction between Los and fructose is not mediated by changes in the renal ACE/ACE2 balance.