Inhibitory effects of captopril on c-myc expression during left ventricular hypertrophy.
OBJECTIVE
To study the molecular mechanism of captopril (Cap) on the inhibition of left ventricular hypertrophy (LVH), disclose the expression and distribution of c-myc in different cell types in left ventricle (LV) in spontaneously hypertensive rats (SHR).


METHODS
Cap 100 mg.kg-1.d-1 was given p.o. to SHR. Systolic blood pressure (SBP), left ventricular weight (LVW), and body weight (BW) were measured at 16-wk old. The level of angiotensin II (Ang II), c-myc mRNA, and oncoprotein were determined by immunohistochemical method, Northern blot, and Western blot, respectively.


RESULTS
Cap reduced SBP, LVW/BW in SHR, with a decrease of Ang II and c-myc expression in LV. Local cardial Ang II mainly distributed in cardiomyocytes. Cap inhibited cardial Ang II production and c-myc expression (histochemical staining intensity index, 0.49 +/- 0.04 vs 0.83 +/- 0.24, P < 0.01). The c-myc oncoprotein was prevailingly located in cardiac fibroblasts. The c-myc oncoprotein in Cap treated SHR was lower than that of WKY.


CONCLUSIONS
High expression of c-myc in fibroblasts played an important role in the development of LVH in SHR. Inhibitory effects of Cap on LVH was associated with a decreased myocardial Ang II and interstitial fibroblasts c-myc expression. The c-myc oncoprotein post-transcriptional translation was also interrupted by Cap.
Su
J Z
JZ
Department of Cardiology, First Affiliated Hospital of Fujian Medical University, Fujian Institute of Hypertension, Fuzhou, China. sujinzi@163.net
Chen
D G
DG
Wu
K G
KG
Chen
S C
SC
Hu
W Y
WY
Wang
X Y
XY
Rui
H B
HB
Wang
H J
HJ
Xu
C S
CS
D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D016259:Genes, myc; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000235:genetics / Q000378:metabolism*; D008297:Male; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000806:Angiotensin-Converting Enzyme Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D000804:Angiotensin II; D002216:Captopril