Mechanical stretch/relaxation stimulates a cellular renin-angiotensin system in cultured rat mesangial cells

Exp Nephrol. Jan-Feb 1998;6(1):57-66. doi: 10.1159/000020505.

Abstract

Angiotensin II (Ang II) may play a significant role mediating intraglomerular hypertension and glomerular sclerosis. Therefore, we investigated whether a model of pressure-induced stress, mechanical stretch/relaxation, affected the renin-angiotensin system (RAS) in cultured rat mesangial cells. Type 1 Ang II receptor (AT1R) expression was assessed by 125I-Ang II binding and quantitative reverse-transcription polymerase chain reaction. Stretch/relaxation increased steady-state AT1R mRNA levels as well as specific [125I]Ang II binding. Increased AT1R expression was associated with altered AT1R signaling. Ang II (100 nM) increased total phosphoinositide hydrolysis in control cells (186 +/- 25%, n = 6; p < 0.025 vs. no treatment). However, stretch/relaxation for 48 h further augmented AT1R-mediated PI hydrolysis (293 +/- 38%, n = 6; p < 0.025 vs. Ang II treatment alone). We examined other RAS components in mesangial cells subjected to stretch/relaxation. Angiotensinogen, determined by radioimmunoassay of Ang I generation in conditioned media, increased with stretch/relaxation, and reverse-transcription polymerase chain reaction demonstrated increased angiotensinogen gene expression in stretch/relaxation-treated cells. However, renin activity and angiotensin-converting-enzyme-like activity were unaffected by stretch/relaxation. Thus, mesangial cells maintain a local RAS similar to those described in other tissues, and AT1R expression and angiotensinogen production in this cellular RAS are increased by stretch/relaxation. It is likely that mesangial cells in vivo, exposed to variations in intraglomerular pressure, may regulate their responses via a local RAS.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin II / metabolism
  • Angiotensin II / pharmacology
  • Angiotensinogen / genetics
  • Animals
  • Biomechanical Phenomena
  • Blotting, Northern
  • Blotting, Southern
  • Cells, Cultured
  • Glomerular Mesangium / cytology*
  • Glomerular Mesangium / physiology*
  • Mechanoreceptors / physiology
  • Peptidyl-Dipeptidase A / metabolism
  • Phosphatidylinositols / metabolism
  • Polymerase Chain Reaction
  • Pressure
  • RNA, Messenger / analysis
  • Rats
  • Receptors, Angiotensin / genetics
  • Renin / metabolism
  • Renin-Angiotensin System / physiology*
  • Stress, Mechanical

Substances

  • Phosphatidylinositols
  • RNA, Messenger
  • Receptors, Angiotensin
  • Angiotensinogen
  • Angiotensin II
  • Peptidyl-Dipeptidase A
  • Renin