Section 10
Chapter 9,002

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

Becker, B.N.; Yasuda, T.; Kondo, S.; Vaikunth, S.; Homma, T.; Harris, R.C.

Experimental Nephrology 6(1): 57-66


ISSN/ISBN: 1018-7782
PMID: 9523174
DOI: 10.1159/000020505
Accession: 009001488

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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.

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