| Left ventricular hypertrophy (LVH) is regarded as an independent risk factor for the morbidity and mortality of essential hypertension (EH). It has been proved that the patients with EH and LVH die of myocardial infarction, heart failure, sudden death and other cardiovascular disease with 6-8 times more chances than that of patients with EH. The pathological basis of LVH includes myocyte hypertrophy, excessive extracellular matrix (ECM) dominantly in collagen accumulation and myocardial fibrosis (MF), which play a key role in pathogenesis of heart failure and arrhythmia in patients with EH. Cardiac fibroblasts (CFs) , which plays a pivotal role in ECM synthesis and degradation, synthesizes and secretes insufficient matrix metalloproteinases (MMPs) with lower capability of breaking down collagen in the cardiac interstitium and participated in the pathogenesis and development of myocardial fibrosis in EH with LVH. To date, the modulating mechanism of degradation of cardiac interstitial collagen by CFs is still unclear. The aim of the study was to investigate the effects of nitric oxide (NO) on MMPs collagenlytic activity, the expression of MMPs and tissue inhibitor of matrix metalloproteinases (TIMPs) and its intracellular signal transduction pathway as well. The study also involved in the effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor atorvastatin on MMPs collagenlytic activity, the expression of MMPs andTIMPs, and its relationship with the expression of inducible nitric oxide synthase(iNOS) mRNA and activity of nitric oxide synthase (NOS)-NO system, so as to find a new way for exploring the etiology and treatment of left ventricular hypertrophy in EH.In the study, isolated and cultured CFs of neonatal Sprague-Dawley(SD) rats were used as experiment model. MMP-1, MMP-2 and MMP-9 gelatinlytic activities were evaluated by zymography. Expression of iNOS, MMP-l, MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 mRNA were determined by reverse transcription-polymerase chain reaction (RT-PCR). NO concentration was measured by nitric acid reductase method, and NOS activities was estimated by spectrophotometry. We observed dynamically: (1) The effects of L-arginine (L-arg) and sodium nitroprusside (SNP) on MMP-1, MMP-2 and MMP-9 gelatinlytic activity, and the expression of MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 mRNA. (2) The effects of NOS inhibitor LNNA, soluble guanylyl cyclase (sGC) inhibitor LY83583, cGMP dependent protein kinase (PKG) agonist 8-cPCT-cGMP and PKG inhibitor KT5823 on MMP-1, MMP-2 and MMP-9 gelatinlytic activity, and the expression of MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 mRNA induced by L-arg and SNP. (3) The effects of atorvastatin on MMP-1, MMP-2 and MMP-9 gelatinlytic activity, the expression of MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 mRNA, and their relationship with the expression of iNOS mRNA and activities of NOS-NO system.The results of the study show that: (l)CFs secretes MMP-1, MMP-2 and MMP-9 in a time-dependent manner under basal conditions. The total gelatinlytic area of MMPs secreted by cultured CFs (1 × 104 cell) were (1.22± 0.12), (2.42±0.13), (3.75±0.17), )5.31±0.13), (6.88±0.26), (10.47±0.17) and (14.50±0.13 ) mm2 at 6h, 12h, 24h, 36 h, 48 h, 60 h and 72h, respectively. The MMP-1 (54kDa) activity, which appears at 12h firstly, account for 4-6% of total MMPs activity. The MMP-2 (58kDa and 62kDa) activity account for 100%, 96.3%, 92.5%, 91.3%, 91.2%, 91.5% and 91.9% of total MMPs activity, respectively. The MMP-9 (92kDa) activity, which appears at 24h firstly, account for 2-3% of total MMPs activity. There were significantly increases in MMP-1, MMP-2 and MMP-9 activities with time prolonged (P<0.01). (2) L-arginine increases MMP-1, MMP-2 and MMP-9 activities in atime-dependent and concentration-dependent manner. There were significantly increases in the gelatinlytic area of MMP-1, MMP-2 and MMP-9 in 10"5mol/L L-arginine group (0.27±0.02, 3.77±0.29 and 0.16±0.02 mm2) than that of control group (0.21±0.
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