Resistance exercise shifts the balance of renin-angiotensin system toward ACE2/Ang 1-7 axis and reduces inflammation in the kidney of diabetic rats

Life Sci. 2021 Dec 15:287:120058. doi: 10.1016/j.lfs.2021.120058. Epub 2021 Oct 18.

Abstract

Aims: We aimed to determine whether resistance training (RT) regulates renal renin-angiotensin system (RAS) components and inflammatory mediators in diabetic rats.

Main methods: Male Wistar rats (3 months old) were randomly assigned into four groups: non-trained (NT), trained (T), non-trained + diabetes (NTD) and trained +diabetes (TD). Diabetes was induced by streptozotocin (50 mg/kg, Sigma Chemical Co., St. Louis, MO, USA), before RT protocol. Trained rats performed RT protocol on a 110-cm ladder (8 ladder climbs, once/day, 5 days/week, 8 weeks), carrying a load corresponding to 50-80% of maximum carrying capacity. Blood glucose, albuminuria and urinary volume were measured. Renal levels of angiotensin peptides (angiotensin I, II and 1-7), inflammatory markers, and also the activities of angiotensin-converting enzyme (ACE) and ACE2 were determined.

Key findings: Blood glucose and urinary volume were elevated in diabetic animals, and RT decreased albuminuria, renal Ang I and Ang II levels in diabetic rats. RT shifted the balance of renal RAS toward ACE2/Ang 1-7 axis in TD group, and mitigated the high levels of interleukin (IL)-10, IL-1β and cytokine-induced neutrophil chemoattractant 1 (CINC) in the context of diabetes. Strong positive correlations were found between albuminuria and Ang II, IL-10 and IL-1β. On the other hand, intrarenal Ang 1-7 levels were negatively correlated with IL-10 and IL-1β levels.

Significance: RT improved kidney function by modulating intrarenal RAS toward ACE2/Ang 1-7 axis and inflammatory cytokines. RT represents a reasonable strategy to improve the renal complications induced by diabetes, counteracting nephropathy-associated maladaptive responses.

Keywords: Cytokines; Diabetes; Diabetic nephropathy; Inflammation; Renin angiotensin system; Resistance training.

MeSH terms

  • Angiotensin I / metabolism*
  • Angiotensin-Converting Enzyme 2 / metabolism*
  • Animals
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / therapy
  • Kidney / metabolism
  • Male
  • Nephritis / metabolism*
  • Nephritis / therapy
  • Peptide Fragments / metabolism*
  • Rats
  • Rats, Wistar
  • Renin-Angiotensin System / physiology*
  • Resistance Training / methods*

Substances

  • Peptide Fragments
  • Angiotensin I
  • Ace2 protein, rat
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)