Angiotensin II enhances glomerular expression of a nonmuscle myosin heavy chain, SMemb, with extracellular matrix accumulation.
OBJECTIVE
We previously showed that the mesangial expression of nonmuscle-type myosin heavy chain, SMemb, was related to glomerular sclerosis. Although angiotensin II (AII) is known to promote the glomerular accumulation of extracellular matrix and sclerosis, the effect of AII on the mesangial expression of SMemb is unknown. Thus, we investigated the effect of AII on the mesangial expression of SMemb and synthesis of fibronectin.


METHODS
We continuously administered AII to Sprague-Dawley rats with subcutaneous osmotic minipumps for 14 days. Control animals received normal saline instead. The effects of oral administration of an AII type 1 (AT1) receptor antagonist, candesartan cilexetil, and a vasodilator, hydralazine, were also examined.


RESULTS
Semiquantitative immunohistochemical evaluation and Western blot analysis showed that AII significantly enhanced glomerular expression of SMemb (0.87 +/- 0.33 vs. 0.40 +/- 0.19 for immunohistochemical grading, p < 0.05; 2.55 +/- 0.88 vs. 1.16 +/- 0.75 for Western blot analysis, p < 0.05). Glomerular fibronectin was also increased in AII-administered rats (301.7 +/- 206.8 ng/5 microg protein vs. 95.8 +/- 81.3 ng/5 microg protein, p < 0.05). Candesartan cilexetil attenuated these effects. On the other hand, hydralazine did not change the glomerular expression of SMemb enhanced by AII administration.


CONCLUSIONS
All induced a phenotypic alteration in mesangial cells, enhanced the mesangial expression of SMemb and stimulated the fibronectin synthesis. These results suggest that the mesangial expression of SMemb is related to glomerular matrix accumulation and that AII mediates both mesangial processes via AT1 receptors.
Mise
Naobumi
N
Second Department of Internal Medicine, Faculty of Medicine, Gunma University, Maebashi, Japan.
Kimura
Kenjiro
K
Kurabayashi
Masahiko
M
Nagai
Ryozo
R
Okuda
Toshihiro
T
Ohba
Shigeyoshi
S
Suzuki
Naoe
N
Miyashita
Kazuhisa
K
Kamijo
Atsuko
A
Tojo
Akihiro
A
Goto
Atsuo
A
Omata
Masao
M
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D024501:Nonmuscle Myosin Type IIB; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism
D005353:Fibronectins; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains