Mechanisms of hypertension in transgenic rats expressing the mouse Ren-2 gene.
Mechanisms of hypertension in transgenic rats expressing the mouse Ren-2 gene.
复制标题
表达小鼠 Ren-2 基因的转基因大鼠的高血压机制。
DOI：
10.1152/ajpregu.1994.266.4.r1273
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Ferrario,CM
中科院分区：
文献类型：
--
作者：
Moriguchi,A;Brosnihan,KB;Kumagai,H;Ganten,D;Ferrario,CM
转鼠Ren-2基因（Ren-2d）27转基因（TG）大鼠是新近建立的一种单基因高血压动物模型。为了深入了解这种形式的高血压的机制，我们确定了氯沙坦（10 mg/kg）或赖诺普利（20 mg/kg）治疗13天对成熟雌性TG高血压大鼠和SD大鼠的血压（BP）和血浆血管紧张素（ANG）肽水平的影响。通过全身注射NG-单甲基-L-精氨酸（L-NMMA）或内皮素-1评价内皮源性一氧化氮（NO）对维持高血压和治疗反应的贡献。TG大鼠的高血压与血浆ANG I降低有关，血浆ANG II无差异，血浆ANG-（1-7）接近可检测水平。在TG高血压和正常血压对照组中，赖诺普利比氯沙坦更能降低血压。在两种品系中，赖诺普利引起的血压慢性下降伴随着血浆ANG I和ANG-（1-7）的显著增加，而氯沙坦增加了两种品系中的血浆ANG I和ANG II以及TG大鼠的血浆ANG-（1-7）。在SD对照组中，抑制NO合酶逆转了赖诺普利或氯沙坦引起的血压下降。与此相反，给予L-NMMA的TG大鼠给予相同的治疗没有。氯沙坦和赖诺普利可减弱TG大鼠全身注射内皮素-1引起的短暂内皮介导的舒张相降压反应。这些研究表明雌性TG大鼠的高血压是由RAS介导的。（250字处删节）
Transgenic (TG) rats carrying the mouse Ren-2 gene (Ren-2d)27 are a newly established monogenetic model in hypertension research. To gain an insight into the mechanisms of this form of hypertension we determined the effects of a 13-day therapy with losartan (10 mg/kg) or lisinopril (20 mg/kg) on the blood pressure (BP) and plasma levels of angiotensin (ANG) peptides of mature female TG hypertensive and Sprague-Dawley (SD) rats. The contribution of endothelium-derived nitric oxide (NO) to the maintenance of their hypertension and the response to therapy was evaluated by systemic injection of either NG-monomethyl-L-arginine (L-NMMA) or endothelin-1. Hypertension in TG rats was associated with decreased plasma ANG I, no differences in plasma ANG II, and plasma ANG-(1-7) near the detectable level. Lisinopril lowered BP more than losartan in both TG hypertensive and normotensive controls. In both strains, the chronic fall in BP produced by lisinopril was accompanied by significant increases in plasma ANG I and ANG-(1-7), while losartan augmented plasma ANG I and ANG II in both strains and plasma ANG-(1-7) in TG rats. Inhibition of NO synthase reversed the fall in BP produced by either lisinopril or losartan in SD controls. In contrast, administration of L-NMMA to TG rats given the same therapy did not. The transient endothelium-mediated relaxing phase of the depressor response to systemic injections of endothelin-1 was attenuated by losartan and lisinopril in TG rats. These studies indicate that hypertension in female TG rats is mediated by the RAS.(ABSTRACT TRUNCATED AT 250 WORDS)