Macrophage and myofibroblast proliferation in remnant kidney: role of angiotensin II.
Local macrophage proliferation has been shown to be a major mechanism of macrophage accumulation in several immunologically-induced animal models of renal diseases. This study has explored whether local proliferation of macrophages and myofibroblasts contribute to their accumulation in rat remnant kidney model and investigated the role of angiotensin II (Ang II) in these cellular pathological events by blocking the angiotensin II activity with ramipril, and angiotensin converting enzyme (ACE) inhibitor, or valsartan, an Ang II type 1 receptor antagonist. There was local proliferation of macrophages and myofibroblasts within renal parenchyma following renal ablation, contributing significantly to macrophage and myofibroblasts accumulation, renal dysfunction and fibrosis. Both treatment resulted in inhibition of local proliferation of macrophages and myofibroblasts and this was associated with attenuation of renal injury. In conclusion, inhibition of local macrophage and myofibroblast proliferation may be an important mechanism by which Ang II blockade attenuated renal injury following renal ablation.
Wu
L L
LL
Department of Medicine, Austin and Repatriation Medical Center, Victoria, Australia. wu@austin.unimelb.edu.au
Yang
N
N
Roe
C J
CJ
Cooper
M E
ME
Gilbert
R E
RE
Atkins
R C
RC
Lan
H Y
HY
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology*; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D000804:Angiotensin II