| Insulin resistance and hyperinsulinemia have been correlated with hypertension, type 2 diabetes mellitus, obesity and atherosclerosis, the mechanisms responsible for the increased cardiovascular risk associated with insulin are not completely understood. It has been established that increased activity of the renin-angiotensin system (RAS) is associated with increased cardiovascular risk, hypertensive individuals are more likely to be insulin resistance, angiotensin-converting enzyme inhibitors not only reduce blood pressure but also restore insulin sensitivity, thereby reducing cardiovascular disease complications. Thus, it is possible that an interaction between insulin and the RAS may account for many high-risk cardie conditions. However, the combined effects of insulin and the RAS on vascular function have not been fully evaluated. This study based on animal model and cell culture to examine the relationship between RAS and insulin resistance pathogenesis.Objective: (1)To investigate the role of angiotensin II (Ang II), nitric oxide(NO) and superoxide anionfCV) in hypertension pathogenesis. (2)To study the changes of serum Ang II, NO and 02" in hyperinsulinemia rat. (3)To investigate the effects of glucose and insulin on human umbilical vein endothelial cells(HUVEC) secreting Ang II, NO and O2-. (4)To test the effects of L-arginine and L-NAME on HUVEC secreting Ang II, NO and O2-. (5)To assess the effects of BH4 on HUVEC secreting Ang II, NO and O2-. (6)To observe the feature of Ang II generation pathways in HUVEC. (7)To examine the influences of situ Ang II formation on HUVEC generating NO and 02".(8)To investigate Ang II and insulin IP3/Ca2+ signaling system in human umbilical artery smooth muscle cells.Methods: In the fist part of animal experiment, we tied rat left renal artery to set up hyper-renin model, blood pressure, heart rate were measured and serum Ang II, NO, O2- level were tested. In another animal experiment, rats were fed glucose rich diet for 8-16 weeks, to observe the changes of blood pressure, heart rate, body weightand serum Ang II, NO, O2- level. In the part of cell culture, we investigated the effects of glucose and insulin on HUVEC secreting Ang II, NO, O2- and the influences of L-arginine, L-NAME and BH4 respectively as well. We also investigated the influences of angiotensin converting enzyme(ACE) and chymase on HUVEC generating Ang II, NO and O2-. Last, we investigated Ang II and insulin IP3/Ca2+ signaling system in human umbilical artery smooth muscle cells(HUASMC). NO was tested by nitric acid reductase method, SOD activity used xanthine oxidase method, 02" was tested based on fenton raction, cGMP, Ang II ,IP3 and CaM was used radio-immunity assay.Results: Systolic blood pressure was higher in ligature group than that in control group (p<0.05), systolic blood pressure was much lower in ligature+Losartan group than that in ligature group, systolic blood pressure was higher in ligature+L-arginine group than that in control group, but lower than ligature group. Heart rate did not change significantly after experiment (p>0.05). Ang II was higher in ligature group as compared with control group, even much higher in ligature+Losartan group(p<0.01). The level of cGMP in ligature group lower than that in control group, ligature+L-arginine+losartan group higher than that in ligature group(p<0.05). The concentration of NO was lower in ligature group (p<0.05), NO was higher in ligature+L-Arg+Losartan group than that in ligature group (p<0.05). O2- was higher in ligature group and ligature+L-Arg group than that in control group (p<0.05), 02" was lower in ligature+Losartan group than that in ligature group (p<0.05). SOD activity was lower in ligature group than that in control group (p<0.05), higher in ligature+L-Arg group and ligature+L-Arg+Losartan group than that in ligature group (p<0.05).Eight and sixteen weeks after experiment, although blood glucose did not change significantly, but blood pressure, body weight and serum insulin elevated in glucose rich diet rats, in spite...
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