Role of mitogen-activated protein kinase in the inhibition of myocardial hypertrophy by nitric oxide in renovascular hypertensive rats
10.3321/j.issn:0371-0874.2001.01.009
- VernacularTitle:MAPK信号途径在一氧化氮抑制大鼠心肌肥大中的作用
- Author:
Wei LU
1
;
Pei-Qing LIU
;
Ting-Huai WANG
;
Su-Zhen GONG
;
Shi-Gan FU
;
Jing-Yun PAN
Author Information
1. Sun Yat-Sen University of Medical Sciences
- From:
Acta Physiologica Sinica
2001;53(1):32-36
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this study was to examine the effects of L-arginine, a nitric oxide (NO) precursor, on protein expression of endothelial nitric oxide (eNOS), nitrite/nitrate content, protein expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) and the activity of mitogen-activated protein kinase (MAPK) in cardiac tissues in renovascular hypertensive rats (RHR). The Goldblatt renovascular hypertensive model was established by two-kidney one clip method. The rats were divided into four groups, respectively treated with 50, 150 and 450 mg/kg L-arginine and 150 mg/kg L-arginine plus 10 mg/kg L-NAME (an eNOS inhibitor) (ip). Another group did not receive specific treatment from the 5th week after renal artery constriction. Control group was sham-operated. Mean arterial blood pressure (MABP) and the ratio of left ventricular weight to body weight (LVW/BW) were measured 8 weeks after treatment. eNOS protein expression, nitrite/nitrate content, MKP-1 protein expression and MAPK activity in cardiac tissues were detected using Western blot analysis, enzyme-reduction method and substrate in-gel kinase assay, respectively. It was found that L-arginine significantly inhibited the increase of MABP and LVW/BW, attenuated the activity of MAPK, increased protein expression of eNOS and MKP-1 and potentiated production of NO in cardiac tissue with the most effective dosage of 150 mg/kg, and these effects of L-arginine could be inhibited by L-NAME. These results suggest that MKP-1 may play an important role in the NO-induced inhibition of myocardial hypertrophy. The anti-hypertrophic effects of L-arginine may involve increase of eNOS protein expression and NO production, poten- tiation of MKP-1 protein expression, and inhibition of MAPK activity in the cardiac tissue of RHR.
