| Cardiomyocyteapoptosis and genomic polymorphisms in sinoaortic-denervated ratsBlood pressure (BP) is not constant during 24h. The spontaneous variation in BP is defined as "blood pressure variability" (BPV). Rats with chronic sinoaortic denervation (SAD) exhibit a high BPV and a normal BP level. In our previous studies, it was found that SAD produced a remarkable cardiovascular remodeling. It is known that apoptosis plays an important role in myocardial remodeling in hypertension. However, it's not yet clear about the role of apoptosis in myocardial remodeling in SAD rats. Essential hypertension is complex, multifactorial, genetic susceptibile, as well as environmental factorial disease. With the advent of molecular genetics technologies, over the past 10 years, several candidate genes have been identified in hypertension. However, little is known about these candidate genes in SAD rats. In the present studies, we used SAD rats as a model for high BPV to study the following issues: CD Does apoptosis occur in left ventricle from SAD rats? ? Is expression of apoptosis-related genes changed by SAD? ? What is the possible mechanism of cardiomyocyte apoptosis in SAD rats? (4) What is the effect of ACEI on apoptosis of SAD rats? ? Does there exist genomic DNA polymorphisms in SHR and SAD rats?Methods:SAD or sham-operation (Sham) was performed in male SD rats at the age of 10 weeks. The apoptosis study was performed in SAD and Sham rats 4, 8, 16, 32 weeks after operation. In another study, SAD rats were treated with captopril (lOOmg.kg'.d' p.o.) for 16 weeks (group SAD-Cap) after operation. The morphological changes of hearts were examined by histopathological method. Apoptosis in the left ventricle of SAD rats was identified by electron microscopy (EM) and TUNEL method. Protein products and mRNA of bcl-2, bax, Fas and Fas-L was assessed by quantitative immunohistochemistry and RT-PCR. Microsatellite DNA- PCR and RAPD-PCR were used to detect DNA polymorphisms in SHR and SAD rats.Results:—VIIII.SAD rats exhibited a loss in body weight and an increase in heart weight and left ventricle wall compared with age-matched Sham rats.2.Compared with Sham groups, the plasmatic concentrations of NO and ACE were lower, the level of TNF- a was higher, and that of Ang II was unchanged in SAD groups. But the contains of Ang II, ACE, TNF- a in myocardium were higher in SAD rat than in sham rats.3.Myocardium and small arterial walls were found normal in 4-week Sham rats. In SAD 4 weeks, swelling, necrosis, hypertrophy and breaking myocardial fibers in myocardial tissues were observed by routine light microscopy. There was an increase and hypertrophy of interstitial cells, which appeared to consist mostly of bistiocytes, fewer lymphocytes and hypertrophied interstitial connective tissue cells. There was also mild interstitial edema. Focal bleeding of the heart could be seen in SAD rats. In Sham groups at 8,16 and 32 weeks, there was also mild interstitial edema, myocyte hypertrophy, and fibrous tissue around blood vessels in most of heart. SAD rats had remarkable cardiovascular injuiy. In addition, myocardial hypertrophy with thickening of myocardial fibers could be found in most SAD rats. All hearts displayed an apparent increase in the production of matrix material, and focal interstitial fibrosis. The fibrosis in some SAD rats was more pronounced near the endocardium. The interstitial changes were associated with obvious myocyte hypertrophy and focal myocyte degeneration. A progressive hyalinization and thickness of media of coronary artery, perivascular fibrosis and interstitial fibrosis were observed in SAD rats. There were swelling, necrosis and mononuclear infiltration in myocardial tissues. Moreover, Focal fibrillar scar which replaced the damaged myocytes were found at 16 and 32 weeks rats after SAD.4.Ultrastructural examination showed normal myocardium and small arterial walls in Sham group at 4 weeks. The cytoplasm was almost completely occupied by myofibrils and mi...
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