[Role of mitogen-activated protein kinase in the inhibition of myocardial hypertrophy by nitric oxide in renovascular hypertensive rats].
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) (i.p.). 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, potentiation of MKP-1 protein expression, and inhibition of MAPK activity in the cardiac tissue of RHR.
Lu
W
W
Department of Physiology, Sun Yat-Sen University of Medical Sciences, Guangzhou 510089.
Liu
P Q
PQ
Wang
T H
TH
Gong
S Z
SZ
Fu
S G
SG
Pan
J Y
JY
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D002312:Cardiomyopathy, Hypertrophic / Q000209:etiology / Q000517:prevention & control*; D018797:Cell Cycle Proteins; D054638:Dual Specificity Phosphatase 1; D006978:Hypertension, Renovascular / Q000150:complications / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases