Regulation Of Angiotensin Ii Receptor Antagonist On The Receptor

As a new type antihypertensive drug, two typical drugs (Losartan and Valsartan) have received great appreciations ever since they came into market. Their actions are more absolute than ACEI , the Angiotensin-Converting-Enzyme- Inhibitor, which has the adverse effects (such as cough, angioedema) .But their long effects and mechanisms still wait to be studied for their short-use history. We in this book are to observe the regulations of Losa.rtan and Valsartan on the expressions of the mRNA of angiotensin II type 1 receptorsy and discuss their mechanisms of antihypertension. The experiment includes three parts as followed: First: To improve the animal model of rat renal hypertension and investigate the effects of Losartan. Methods: 21 male Spraque-Dauley (SD) rats were devided into three groups at random (the sham-operation group, the Losartan-Qperation group and the model group, 7 each) . Silk thread and a very fine steel wire were used instead of the traditional silver chips to construct the rat 2K1 C renovascular hypertension model and the blood pressure was measured by tail-cuff method. Losartan was dosed at 10mg/Kg at 1 9th day. Then the effects of Losartan on blood pressure and cardiac index (valued as the ratios of the heart-weight to body weight, that is HW/BW) were observed. Second: we used Reverse-Transcription-Polymerase-Chain-Reaction (RT-PCR) method to quantify the expression levels of AT1, mRNA ATIb mRNA in the myocardium and the ischemic kidney (left kidney) and the regulations of Losartan on the subtypes mRNA expressions were studied. We also discussed the poles of the AT, and ATIb receptor in the mechanisms that renovascular hypertension forms and Losartan?s antihypertensive effect. Third: the clinical parts. 10 primary hypertensive patients were chosen at random and therapied by Valsartan. White blood cells(WBC) were separated from the peripheral blood and the AT1 on the WBC was used as the target for its linking to the AT1 receptor on the vascular. RT-PCR method was applied to quantitify the expression of AT1mRNA of the WBC and the changes were studied between pretherapy and posttherapy by Varsartan. Results and conclusion: ①Rat 2K℃ renovascular hypertensive model can be successfully built by using silk and fine steel instead of silver chips. The BP of the model increased markedly in 1 week orso, and stabled after 2 weeks. Myocardial hypertrophy forms in about 4 weeks. Myocardial hypertrophy was evident in the MO (Model)group with a marked higher cardiac index than that of the SO (Sham- Operation) group while insignificant in the LO (Losartan-Operation) group with an undistinguished cardiac index from that of the SO group (p>0.05). Losartan can reverse the high BP level of the model, also the myocardial hypertrophy. ②During the time hypertension forms, the mRNA of ATI receptor subtypes of the myocardial and ischemic kidney change differently, which suggests AT1 of these two tissues were regulated by different styles. The ATIb mRNA of the myocardial added significantly after Losartan's therapy, while not the case is AT1, mRNA. It means that the Losartan's antihypertension mechanism was its blockade of the AT1, receptor. Losartan cannot reverse the upregulation of AT, mRNA and ATIb mRNA of the ischemic kidney, which suggestes that Losartan's antihypertension is for its blockade the AT1 of the myocardial, not the kidney. ③Valsartan has a good effect of antihypertension. It can reduce the AT1 mRNA of white blood cells in primary hypertension pa...