Over-expression of extracellular signal-regulated kinase in vascular smooth muscle cell of hypertensive rats / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate whether extracellular signal-regulated kinase (ERK1/2) was involved in changes of vascular smooth muscle cell (VSMC) under hypertension.</p><p><b>METHODS</b>Two-kidney one clip Wistar hypertensive rats (WHR) were sacrificed and their right kidneys were harvested 4 weeks after surgery. The spontaneously hypertensive rats (SHR) were divided into 4, 8, and 16 weeks old groups (SHR4w, SHR8w, and SHR16w), respectively. The control group were sham operated age-matched Wistar rats. Immunohistochemical technique and Western blotting were applied to study ERK1/2 protein expression in VSMC of the renal vascular trees in WHR, SHR, and control rats.</p><p><b>RESULTS</b>Blood pressure in two-kidney one clip WHR obviously increased at one week after surgery, and reached to 198. 00 +/- 33. 00 mm Hg at the end of experiment, significantly higher than that in the control rats (P < 0.01). Blood pressure in SHR4w (108.00 +/- 11.25 mm Hg) was similar to that in the controls. However, it rose to 122.25 +/- 21.75 mm Hg in SHR8w, and even up to 201.75 +/- 18.00 mm Hg in SHR16w, which were significantly higher than that of both the SHR4w and the controls (P < 0.01). The rate and degree of glomerular fibrosis in WHR were significantly higher than controls (P < 0.05). Hyaline degeneration of the afferent arterioles was found in WHR. In contrast, either fibrosis of glomerulus or hyaline degeneration of the arterioles or protein casts was not observed in SHR4w, SHR8w, and SHR16w. Immunohistochemical staining results showed expression of ERK1 was similar to that of ERK2. The positive rates of ERK2 staining in VSMC of afferent arterioles, interlobular, interlobar, and arcuate arteries in two-kidney one clip WHR were significantly higher (7.09% +/- 1.75%, 14.57% +/- 4.58%, 29.44% +/- 7.35%, and 13.63% +/- 3. 85%, respectively) than that of the controls(P < 0.01). The positive rates of ERK2 staining in VSMC at afferent arterioles, interlobular, interlobar, and arcuate arteries in SHR16w were significantly higher (12.09% +/- 1.40%, 24.17% +/- 6.92%, 32.44% +/- 4.05%, and 18.61% +/- 3.35%, respectively) than that of the controls (P < 0.01), too. The expression of ERK1/2 protein of kidney in WHR and SHR16w was significantly higher than that in the controls by Western blotting assay (P < 0.01).</p><p><b>CONCLUSION</b>Extracellular signal transduction system are highly expressed in kidney VSMC of two-kidney one clip WHR and SHR. Phospho-ERKI/2 may play an important role in VSMC hypertrophy and hyperplasia under hypertension.</p>

P21ras and phosphorylated extracellular signal-regulated protein kinase are highly expressed in vascular smooth muscle cells of hypertensive rats / 南方医科大学学报

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>