[Effect of tashinone on nitric oxide synthase in hypertrophic cardiomyocyte of rats suffered abdominal aorta constriction].
OBJECTIVE
To explore the molecular biological mechanism for tanshinone II A reversing left ventricular hypertrophy, it would be studying the effect of tashinone on the endothelial nitric oxide synthase (eNOS) and protein kinase C (PKC) in the hypertrophic cadiocyte of rats suffered abdominal aorta constriction.


METHODS
SD rats were operated with abdominal aorta constriction and 8 rats were done with sham surgery. After 4 weeks, all rats were divided into 4 groups: myocardial hypertrophy group, low dose tanshinone II A group (10 mg x kg(-1) x d(-1)), high dose tanshinone II A group (20 mg x kg(-1) x d(-1)) and valsartan group (10 mg x kg(-1) d(-1) intragastric administration). 8 weeks later, the rats were used to measure the left ventricular mass index (LVMI) with the tissue of left ventricle and myocardial fiber dimension (MFD) by pathological section and HE stain, to detect the nitric oxide content by nitrate reductase, to detect the genic expression of eNOS by RT-PCR and to detect the activity of protein kinase C (PKC) by Western blotting.


RESULTS
1) The blood pressure in group myocardial hypertrophy [(186 +/- 13) mmHg] and tansginone II A [low and high dose (188 +/- 11,187 +/- 14) mmHg] was obviously higher than that in group sham surgery and valsartan group [vs (117 +/- 8, 136 +/- 15) mmHg, P < 0.01]. But there was no difference between group myocardial hypertrophy and group tanshinone II A (low and high dose). 2) The LVMI and MFD were obviously higher in group tanshinone II A low and high dose) and group valsartan than those in group sham surgery (P < 0.05), and lower than those in group myocardial hypertrophy (P < 0.01). 3) The NO level was obviously higher in group tanshinone II A (low and high dose) and group valsartan than that in group myocardial hypertrophy (12.78 +/- 1.66, 11.95 +/- 1.39, 12.26 +/- 2.08 vs 5.83 +/- 1.06) micromol x L(-1), (P < 0.01 ), and lower than that in group sham surgery (vs 19.35 +/- 1.47) micromol x L(-1), (P < 0.05). 4) The expressive level of eNOS mRNA and protein in myocardial hypertrophy group was less than that in other groups (P < 0.01). And valsartan group was less than tanshinone II A groups and sham surgery group (P < 0.05), but there were no difference among the two tanshinone II A groups and sham surgery group. 5) The level of PKC protein in group myocardial hypertrophy was obviously higher than that in all the other groups (1.291 +/- 0.117 vs 0.563 +/- 0.094, 0.605 +/- 0.051, 0.519 +/- 0.062, 0.827 +/- 0.086, P < 0.01), and the level in group valsartan was higher than that in group sham operation and group tanshinone II A (low and high dose).


CONCLUSIONS
NO/NOS system in local myocardium has close relationship with the pathological process for myocardial hypertrophy. Tanshinone II A can produce the pharmacological action to reverse myocardial hypertrophy by inhibiting the activity of PKC and promoting the genic expression of eNOS in local myocardium and the production of endogenous NO.
Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. ysli@tjh.tjmu.edu.cn
Yong-sheng
YS
Li
Zhao-hua
ZH
Wang
Li
L
Yan
Yong-quan
YQ
Yong
Jin
J
Wang
Qian-sheng
QS
Liang
Zhi
Z
Zheng
Guang-tian
GT
Yang
D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology; D001572:Benzofurans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology; D003251:Constriction, Pathologic / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D001572:Benzofurans; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; C530742:tashinone IIA; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C