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Angiotensin II receptor blockade inhibits acute glomerular injuries with the alteration of receptor expression.
Lab Invest. 2009 Feb; 89(2):164-77.LI

Abstract

Angiotensin II receptor blockade (ARB) suppresses the progression of chronic kidney disease. However, the renoprotective effect of ARB in the active phase of glomerulonephritis (GN) has not been evaluated in detail. We examined the alteration of angiotensin II receptors' expression and the action of ARB on acute glomerular injuries in GN. Thy-1 GN was induced in rats that were divided into three groups (n=7, in each group); high dose (3 mg/kg/day) or low dose (0.3 mg/kg/day) olmesartan (Thy-1 GN+HD- or LD-ARB group), and vehicle (Thy-1 GN group). Renal function and histopathology were assessed by week 2. In the Thy-1 GN group, diffuse mesangiolysis and focal aneurysmal ballooning developed by day 3. Marked mesangial proliferation and activation progressed with glomerular epithelial injury. We confirmed that both angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R) were expressed on glomerular endothelial, mesangial, epithelial cells, and macrophages, and increased 7 days after disease induction. However, ARB treatment caused a decrease in AT1R and a further increase in AT2R expression in glomeruli. ARB prevented capillary destruction and preserved eNOS expression after diffuse mesangiolysis. Mesangial proliferation and activation was suppressed markedly with low levels of PDGF-B expression. Glomerular desmin expression, which is a marker for injured glomerular epithelial cells, was diminished significantly with retained expression of nephrin and podoplanin. Glomerular macrophage infiltration was also inhibited. Proteinuria was suppressed significantly. Furthermore, these effects of ARB showed dose dependency. These results provide insights that ARB affects individual glomerular cells and macrophages through angiotensin II receptors, with the alteration of both AT1R and AT2R expressions, and leads to inhibition of the acute destructive and proliferative glomerular lesions in GN.

Authors+Show Affiliations

Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19139720

Citation

Mii, Akiko, et al. "Angiotensin II Receptor Blockade Inhibits Acute Glomerular Injuries With the Alteration of Receptor Expression." Laboratory Investigation; a Journal of Technical Methods and Pathology, vol. 89, no. 2, 2009, pp. 164-77.
Mii A, Shimizu A, Masuda Y, et al. Angiotensin II receptor blockade inhibits acute glomerular injuries with the alteration of receptor expression. Lab Invest. 2009;89(2):164-77.
Mii, A., Shimizu, A., Masuda, Y., Ishizaki, M., Kawachi, H., Iino, Y., Katayama, Y., & Fukuda, Y. (2009). Angiotensin II receptor blockade inhibits acute glomerular injuries with the alteration of receptor expression. Laboratory Investigation; a Journal of Technical Methods and Pathology, 89(2), 164-77. https://doi.org/10.1038/labinvest.2008.128
Mii A, et al. Angiotensin II Receptor Blockade Inhibits Acute Glomerular Injuries With the Alteration of Receptor Expression. Lab Invest. 2009;89(2):164-77. PubMed PMID: 19139720.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin II receptor blockade inhibits acute glomerular injuries with the alteration of receptor expression. AU - Mii,Akiko, AU - Shimizu,Akira, AU - Masuda,Yukinari, AU - Ishizaki,Masamichi, AU - Kawachi,Hiroshi, AU - Iino,Yasuhiko, AU - Katayama,Yasuo, AU - Fukuda,Yuh, Y1 - 2009/01/12/ PY - 2009/1/14/entrez PY - 2009/1/14/pubmed PY - 2009/2/13/medline SP - 164 EP - 77 JF - Laboratory investigation; a journal of technical methods and pathology JO - Lab. Invest. VL - 89 IS - 2 N2 - Angiotensin II receptor blockade (ARB) suppresses the progression of chronic kidney disease. However, the renoprotective effect of ARB in the active phase of glomerulonephritis (GN) has not been evaluated in detail. We examined the alteration of angiotensin II receptors' expression and the action of ARB on acute glomerular injuries in GN. Thy-1 GN was induced in rats that were divided into three groups (n=7, in each group); high dose (3 mg/kg/day) or low dose (0.3 mg/kg/day) olmesartan (Thy-1 GN+HD- or LD-ARB group), and vehicle (Thy-1 GN group). Renal function and histopathology were assessed by week 2. In the Thy-1 GN group, diffuse mesangiolysis and focal aneurysmal ballooning developed by day 3. Marked mesangial proliferation and activation progressed with glomerular epithelial injury. We confirmed that both angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R) were expressed on glomerular endothelial, mesangial, epithelial cells, and macrophages, and increased 7 days after disease induction. However, ARB treatment caused a decrease in AT1R and a further increase in AT2R expression in glomeruli. ARB prevented capillary destruction and preserved eNOS expression after diffuse mesangiolysis. Mesangial proliferation and activation was suppressed markedly with low levels of PDGF-B expression. Glomerular desmin expression, which is a marker for injured glomerular epithelial cells, was diminished significantly with retained expression of nephrin and podoplanin. Glomerular macrophage infiltration was also inhibited. Proteinuria was suppressed significantly. Furthermore, these effects of ARB showed dose dependency. These results provide insights that ARB affects individual glomerular cells and macrophages through angiotensin II receptors, with the alteration of both AT1R and AT2R expressions, and leads to inhibition of the acute destructive and proliferative glomerular lesions in GN. SN - 1530-0307 UR - https://www.unboundmedicine.com/medline/citation/19139720/Angiotensin_II_receptor_blockade_inhibits_acute_glomerular_injuries_with_the_alteration_of_receptor_expression_ L2 - http://dx.doi.org/10.1038/labinvest.2008.128 DB - PRIME DP - Unbound Medicine ER -