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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Blood pressure reduction and diabetes insipidus in transgenic rats deficient in brain angiotensinogen
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Blood pressure reduction and diabetes insipidus in transgenic rats deficient in brain angiotensinogen

机译：缺乏脑血管紧张素原的转基因大鼠的血压降低和尿崩症

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摘要

Angiotensin produced systemically or locally in tissues such as the brain plays an important role in the regulation of blood pressure and in the development of hypertension. We have established transgenic rats [TGR(ASrAOGEN)] expressing an antisense ANA against angiotensinogen mRNA spccifically in the brain. In these animals, the brain angiotensinogen level is reduced by more than 90 and the drinking response to intracerebroventric. ular renin infusions is decreased markedly compared with control rats. Blood pressure of transgenic rats is lowered by 8 mmHg (l mmHg = 133 Pa) compared with control rats. Crossbreeding of TGR(ASrAOGEN) with a hypertensive transgenic rat strain exhibiting elevated angiotensin II levels in tissues results in a marked attenuation of the hypertensive phenotype. Moreover, TGR(ASrAOGEN) exhibit a diabetes insipidus-like syndrome producing an increased amount of urine with decreased osmolarity. The observed reduction in plasma vasopressin by 35 may mediate these phenotypes of TGR(ASrAOGEN). This new animal model presenting long- term and tissue-speciFic down-regulation of angiotensinogen corroborates the functional significance of local angiotensin production in the brain for the central regulation of blood pressure and for tbe pathogenesis of hypertension.
机译：在诸如大脑的组织中全身或局部产生的血管紧张素在调节血压和高血压的发展中起重要作用。我们已经建立了转基因大鼠[TGR（ASrAOGEN）]，在大脑中特异性表达针对血管紧张素原mRNA的反义ANA。在这些动物中，脑血管紧张素原水平降低了90％以上，并且饮酒对脑室内有反应。与对照大鼠相比，血浆肾素输注明显减少。与对照组相比，转基因大鼠的血压降低了8 mmHg（1 mmHg = 133 Pa）。 TGR（ASrAOGEN）与在组织中显示升高的血管紧张素II水平的高血压转基因大鼠品系的杂交导致高血压表型的显着减弱。此外，TGR（ASrAOGEN）表现出尿崩症样综合征，尿量增加，渗透压降低。观察到的血浆降压素减少35可能介导了TGR（ASrAOGEN）的这些表型。这种呈现长期和组织特异性血管紧张素原下调的新动物模型证实了大脑中局部血管紧张素生成对血压的中央调节和高血压发病机制的功能意义。

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