Angiotensin-(1-7) Influences Tryptophan Absorption in the Rat and Mouse Intestine

Abstract

Aim: Components of the renin-angiotensin system are involved in absorption and regulate both fluid and electrolyte transport in the intestinal epithelium. The angiotensin-converting enzyme 2 (ACE2) is a major Angiotensin-(1-7)-forming enzyme, and a key regulator of the homeostasis of dietary tryptophan (Trp). The aim of the present study was to investigate the physiological role of the Ang-(1-7)/Mas pathway in the intestinal tryptophan absorption. Place and Duration of Study: Departamento de Fisiologia e Biofísica. Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. July 2014-August-2015. Methodology: Two models of Mas receptor inhibition were used: treatments, in rats, with the specific Mas receptor inhibitor, the A-779, and Mas receptor knockout (KO) mice; Ang-(1-7) or Ang-(1-7) + A-779 were injected prior Trp infusion. Male Wistar rats (n = 5 in each goup), wild-type (WT) FVB/N mice and Mas (KO) FVB/N mice (n = 4-8 in each group) were anesthetized, and submitted to midline laparotomy to expose, and isolate jejunal loop. Tyrode’s solution (pH 8) containing tryptophan (0. 25 mg%) was infused (0.5 mL and 0.15 min-1 for rats and mice, respectively) into the jejunal loop and samples were taken at 10-min intervals during the 40-min experiment. Results: Tryptophan absorption was determined by the difference between influx and efflux. Ang-(1-7) increased tryptophan absorption in comparison to the control group (0.13 ± 0.03 vs. 0.23 ± 0.0 mg%, P = .01). ACE2 activity in the effluent of jejunal perfusion, and the expression of ACE2 in the tissue of the small intestine were higher in the group that received Ang-(1-7) compared to the control (13.6 ± 1.5 vs. 50.5 ± 4.1 and 0.14 ± 0.0 vs. 0.38 ± 0.05, (P = .001, and P =.003, respectively). Moreover, the effect of Ang-(1-7) on tryptophan absorption was blunted in Mas KO mice, in comparison to WT (9.8 ± 2.6 vs.1.7 ± 3.0). Conclusions: The results of the present study indicate that Ang-(1-7) increases jejunal tryptophan absorption in rats and these changes are associated with increases in ACE2 activity and expression. In Mas KO mice, these actions were blunted. The findings suggest a new mechanism that is dependent on Ang-(1-7)/Mas by which ACE2 modulates tryptophan intestinal absorption.