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Experimental Study On The Effect Of Gene Expression Of Endothelial Derived Nitric Oxide Synthase In The Pathogenetic Mechanisms Of The Local Vasospasm

Posted on:2002-06-26Degree:MasterType:Thesis
Country:ChinaCandidate:Q FuFull Text:PDF
GTID:2144360032952732Subject:Department of Cardiology
Abstract/Summary:PDF Full Text Request
Background: As a common pathological foundation of many kinds of clinic ischemic heart disease, coronary artery spasm plays an important role not only in variant angina but also in unstable angina, myocardial infarction and sudden death. However, the precise mechanism by which the spasm occurs remains unknown. Many factors may be involved in the pathogenesis of coronary spasm. And the essence of coronary spasm may be the vasoconstriction based on the local coronary high reactivity by the stimulation of nerval and humoral factors. Among the study of coronary high reactivity, abnormal sympathetic innervation, smooth muscle hyperaction and endothelial dysfunction are the main points. Clinical studies have demonstrated that the defect of the eNOS gene expression plays a role in the coronary spasm. The deficiency of eNOS has an effect on the synthesis of NO, result in endothelial dysfunction and the induction of coronaiw spasm lastly. So we plan to investigate the relationship between the gene expression of eNOS and coronary spasm. Objection: to investigate the relation between focal vasospasm and the endothelial dysfunction resulted from the reduction of the gene expression of eNOS. And illustrate the effect of gene regulation of eNOS in the pathogenesis of vasospasm. Methods and results: 1. 36 New Zealand white rabbits (18 male and 18 female) with body weight 2.4 0.3kg were subjected to four group: normal group (n=4), sham operation + normal diet group (group 1, n=8), sham operation + hypercholesterol diet group (group2, n=8), operation + normal iet group (group 3, n=8), operation + hypercholesterol diet group (group4, n8). Balloon endothelial denudation was performed in the group 3 and 4. And group 2 and 4 was fed on a hypercholesterol diet. Group land 2 was operated, but not denuded. And group normal, 1 and 3 was fed on a normal diet. After denudation, Erg(0. 2mg), Hist(20 g/kg), L-NM1MA( 100 mol), NTG(1OEJg/kg)were injected respectively in aorta. Angiography was performed before and 1-3 minutes later after denudation. No obvious vasoconstriction was detected. Serum cholesterol level in group 2 and 4 were a statistically significance between group normal, 1 and 2 8 weeks later after denudation. Angiography performed again 8 weeks later, vascular diameters at denuded sites and control sites changed slightly, and were not significant with those at 0 week. Visible vasospasm was induced at the denuded sites in group 4. Histological study demonstrated that vascular intima were thicken at the denuded site in group 2,3 and 4(P<0.001),but their thickness were comparable. 2. Serum NO level was detected before and after induction of vasospasm in 0 week and 8 week later by the way of nitrate reductase. The results indicated that NO level after induction was significantly raised compared with those before induction in every group in 0 week and in group 1 and 2 8 week later (P<0.001). Serum NO concentrations of group 2 and 4 8 week later have significant decline compared with 0 week. The concentration in group2 and 4 was comparable before and after induction 8 week later. Immunohistochemistry of eNOS revealed that positive stain was present in the endothelium, and eNOS expression in group 2 was decreased compared with group normal, group 1 and 3. Little expression was detected in group 4. 3. Analysis of eNOSmRNA expression in the each group was performed with the method of hybridization in situ and Nort...
Keywords/Search Tags:coronary vasospasm, nitric oxide synthase, nitric oxide, endothelial dysfunction, hypercholesterolemia, balloon endothelialdenudation, gene expression
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