Effects of diabetes and hypertension on macrophage infiltration and matrix expansion in the rat kidney.
BACKGROUND
In experimental models of diabetes mellitus, aggravation of renal injury by concomitant hypertension has been described. Inflammatory mechanisms contribute to renal damage in both diseases. We investigated whether hypertension and diabetes mellitus act synergistically to induce macrophage infiltration and matrix expansion in the kidney.


METHODS
Insulin-dependent diabetes mellitus was induced by streptozotocin injections to hypertensive mRen2-transgenic rats (TGR) and normotensive Sprague-Dawley control rats. Quantitative immunohistochemical examination of kidney tissue sections was used to measure macrophage infiltration and matrix expansion. The expression of MCP-1, Osteopontin, RANTES, ICAM-1 and VCAM-1 was evaluated by real-time RT-PCR. The localization of MCP-1 was studied by immunohistochemistry.


RESULTS
Macrophage infiltration was present in the kidney of normotensive diabetic rats. Hypertensive rats exhibited a more marked infiltration of macrophages, regardless of whether diabetes was present or not. Gene expression of ICAM-1, VCAM-1 and RANTES was unaltered whereas Osteopontin and MCP-1 were induced by hypertension. Immunoreactive MCP-1 was slightly increased in diabetic rat kidney podocytes, and more markedly increased in hypertensive animals. Glomerular matrix accumulation was induced by diabetes and hypertension to a similar degree, and was highest in hypertensive, diabetic animals.


CONCLUSIONS
Diabetes mellitus caused a mild, and angiotensin-dependent hypertension a more marked infiltration of macrophages in the kidney. Combination of both diseases led to additive effects on matrix expansion but not on inflammation. Hypertension appears to be a much stronger stimulus for inflammation of the kidney than STZ diabetes, at least in mRen2-transgenic rats.
Hartner
Andrea
A
Children and Youth Hospital, University of Erlangen-Nuremberg, Loschgestrasse 15, D-91054 Erlangen, Germany. andrea.hartner@rzmail.uni-erlangen.de
Veelken
Roland
R
Wittmann
Michael
M
Cordasic
Nada
N
Hilgers
Karl F
KF
D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism*; D006973:Hypertension / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D007678:Kidney Glomerulus / Q000378:metabolism; D008264:Macrophages / Q000473:pathology*; D008297:Male; D053495:Osteopontin; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000378:metabolism
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin