P21ras and phosphorylated extracellular signal-regulated protein kinase are highly expressed in vascular smooth muscle cells of hypertensive rats.
OBJECTIVE
To investigate the molecular mechanisms of vascular smooth muscle cell (VSMC) hyperplasia and extracellular signal-regulated protein kinase 1/2 (ERK 1/2) phosphorylation of VSMCs under the condition of hypertension.


METHODS
Wistar rat models of two kidney-one clip hypertension (2K1C) were established and their right kidneys were harvested 4 weeks after the operation. Immunohistochemistry and Western blotting were performed to detect phospho-ERK1/2 and P21ras protein expression in the VSMCs of the renal arterioles, and the results were compared with those from 16-week-old spontaneous hypertension rats (SHR16) and control rats.


RESULTS
The blood pressure of 2K1C Wistar rats was significantly increased from 104-/+18 mmHg to 198-/+33 mmHg at the end of the experiment, and the blood pressure of SHR16 reached 163-/+23 mmHg, significantly higher than that of the control rats (P<0.01). Compared with the control group, 2K1C rats showed obvious glomerular fibrosis (P<0.05) with hyaline degeneration of the afferent arterioles. In contrast, neither glomerular fibrosis nor hyaline degeneration of arterioles, nor protein cast was observed in SHR16. In 2K1C rats and SHR16, the positivity rates of phospho-ERK1/2 and p(21ras) staining in the VSMCs of the afferent arterioles and the interlobular, interlobar and arcuate arteries was significantly higher than those of the controls (P<0.01), and the expression of phospho-ERK1/2 and P(21ras) protein in the kidney was also significantly higher as revealed by Western blotting (P<0.01).


CONCLUSIONS
High expression of ERK1/2 and P(21ras) in the renal arteriole VSMCs of 2K1C hypertensive rats and SHR may play an important role in VSMC hypertrophy and proliferation in hypertension.
Jing
Li
L
Institute of Immunopathology, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710061, China. jingliluker@163.com
Zhang
Jian-zhong
JZ
Wang
Yi-li
YL
Guo
Feng-ying
FY
D000818:Animals; D015153:Blotting, Western; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis*; D006978:Hypertension, Renovascular / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010766:Phosphorylation; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D016283:Proto-Oncogene Proteins p21(ras)