Angiotensin II type 1 receptor blockers favorably affect renal angiotensin II and MAS receptor expression in patients with diabetic nephropathy

J Renin Angiotensin Aldosterone Syst. 2020 Apr-Jun;21(2):1470320320919607. doi: 10.1177/1470320320919607.

Abstract

Introduction: The aims of this study were to assess the renal expression of angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), and MAS receptor in human type 2 diabetic nephropathy (DN).

Materials and methods: In total, 115 patients diagnosed with DN by renal biopsy were enrolled in this study. The protein expression levels of the AT1R, AT2R, and MAS receptors were assessed by immunohistochemistry.

Results: The protein expression levels of AT1R, AT2R, and MAS receptor in the renal biopsy tissue were correlated with the pathologic classification of DN. Tubulointerstitial AT1R expression in patients of class IIb was significantly stronger than control samples (p < 0.05). Expression of AT2R and MAS receptors were highest with class IIb DN patients. When DN patients were treated with AT1R blocker (ARB), the expression of AT1R was downregulated (p < 0.05), and the MAS receptor was upregulated in tubular interstitial (p < 0.05).

Conclusions: Our results directly observed that renal expression levels of AT1R increase during the early stages of DN, ARB reducing AT1R while increasing MAS receptor. Therefore, ARB should be used as soon as possible in patients with DN.

Keywords: Diabetic nephropathy; angiotensin II type 1 receptor blocker; angiotensin receptor; immunohistochemistry; renal biopsy.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Angiotensin II / biosynthesis*
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Biopsy
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / metabolism*
  • Diabetic Neuropathies / pathology
  • Female
  • Humans
  • Kidney / metabolism*
  • Kidney / pathology
  • Kidney Tubules / metabolism
  • Male
  • Middle Aged
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • Receptor, Angiotensin, Type 1 / biosynthesis
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 2 / metabolism
  • Receptors, G-Protein-Coupled / biosynthesis*
  • Receptors, G-Protein-Coupled / genetics
  • Young Adult

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Receptors, G-Protein-Coupled
  • Angiotensin II