The Effects Of Rosiglitazone On The ENOS MRNA And Protein Of The Hearts Of Spontaneously Hypertensive Rats

Primary hypertension is a kind of non-epidemic disease in the worldwide and it can also threaten the human health and the anticipate life-span. Hypertension is one multiple systematic disease that can affect many organs to deduce organ-relateed symptom. Because of so many reasons, the research in the treatment of hypertension improve from the simple Blood pressure lowering to the protection stage of the target-organ. In present, the mechanism of hypertension is not very clear.In 1988, Reaven summarize many Epidemic knowledge and clinical research and put forward insulin resistance syndrome (IRS), He consider that a series of diseases, inclusion hypertension, hyperlipidemia, obesity, type two diabetes and so on, have a close relation with IR in the body. From then on, the new era of the prevention hypertension comes. There are many clinical and animal research prove that it can reach a good blood pressure lowering effect and target-organ protection effect through correcting IR. It is not so clear whether insulin resistance can deduce hypertension. In the present years, the abnormal function of endothelial cells has important effect in the happenness of the hypertension .Endothelial cells can excrete Nitric Oxide (NO), endothelial nitric-oxide synthase (eNOS), The latter has important function in hypertension. In this study, We give insulin sensitizer, Rosiglitazone, to SHR big rat and observing its blood pressure lowering function and its target organ protection mechanism.MethodChoose 36 male spontaneously hypertensive rats (SHR), age between 7and 8weeks, then divided them into three groups: SHR group, Rosiglitazone group, positive control group. 1. positive control group: put 140mg/L (0.404mmol/L) nifedipine into the rat drinking water. 2. Rosiglitazone group: put 10mg/L (0.021mmol/L) Rosiglitazone into the rat drinking water, that is equal to the 24 hours continuous dose. The whole test time is 8 weeks. In the whole period, we Mesure the rat pressure every week. After test, anaesthesize the rat through aether, excavate the heart, divide the left ventricle cardiac muscle into 3mm×3mm sample. fix the sample 24 hours with 10% neutral formaldehyde buffer, and then dehydrate with the alcohol, make the dip-wax-sample into 4um continuous slice. Measure the eNOS mRNA and protein expression level in SHR rat through situ-hybrid and Immunohistochemical method. ResultThrough Rosiglitazone and nifedipine treatment, SHR rat pressure begin to reduce in the second week and the mean blood pressure lowering range is high up to 20-25mmHg,. From the forth week on, the reducing function of Rosiglitazone is equal to nifedipine, and this effect can last to the end of the test. In the whole period, the function of Rosiglitazone is more smooth than nifedipine.eNOS has the same change trend in the situ-hybrid and immunohihistochemical method. The main dyed cells in the cardiac muscle slice picture is the the vessel endothelial cells between the muscle. Under the high and low multiple, the dyed cells is fewer and the color is much superficial, light snuff color. The dyed cells in the Rosiglitazone treated rat muscle through situ-hybrid and immunohihistochemical method has higher proportion and are more intense. Nifedipine group is the middle.ConclusionBoth Nifedipine and Rosiglitazone have the function to reduce pressure, the effect of the latter is more slowly than the former but more smooth and lower dose of the latter has the same function. This study show that Rosiglitazone has the function to reduce pressure, and it has more smooth effect and lower dose than the conventional calcium channel blocker-nifedipine. In some extent, Rosiglitazone can displace or combine nifedipine to reduce pressure.Situ-hybrid and immunohihistochemical method result show that the vessel endothelial cells in SHR rat have low eNOS mRNA and eNOS expression level. After the treatment of EOsiglitazone, this stage is alleviated in some extant, Nifedipine has the same function.but more lighter. From this, we know that Nifedipine and Rosiglitazone maybe affect the expression of eNOS receptor so that to protect the cardiac muscle and the function of the latter is more obvious. From this, we can suppose that insulin resistance can be alleviated after the treatment of Rosiglitazone to resume the function of eNOS and vessel endothelial cells, the major is that the function of NO synthesis and release can be resumed to reduce pressure, reduce heart burden and alleviate the contraction of cardiac musule, a series of trauma mechanism.