Mechanical stretch/relaxation stimulates a cellular renin-angiotensin system in cultured rat mesangial cells.
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.
Becker
B N
BN
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2372, USA.
Yasuda
T
T
Kondo
S
S
Vaikunth
S
S
Homma
T
T
Harris
R C
RC
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D001696:Biomechanical Phenomena; D015152:Blotting, Northern; D015139:Blotting, Southern; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000166:cytology* / Q000502:physiology*; D008465:Mechanoreceptors / Q000502:physiology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011312:Pressure; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011945:Receptors, Angiotensin / Q000235:genetics; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D013314:Stress, Mechanical
D010716:Phosphatidylinositols; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012083:Renin