Campbell D J, Rong P, Kladis A, Rees B, Ganten D, Skinner S L
St Vincent's Institute of Medical Research, Fitzroy, Australia.
Hypertension. 1995 May;25(5):1014-20. doi: 10.1161/01.hyp.25.5.1014.
The transgenic TGR(mRen-2)27 rat, in which the Ren-2 mouse renin gene is transfected into the genome of the Sprague-Dawley rat, develops severe hypertension at a young age that responds to inhibitors of angiotensin-converting enzyme and to antagonists of the type 1 angiotensin II (Ang II) receptor. Despite this evidence that the hypertension is Ang II dependent, TGR(mRen-2)27 rats have suppressed renal renin and renin mRNA content, and there is controversy concerning the plasma levels of renin and Ang II in these rats. We investigated the effect of the transgene on circulating and tissue levels of angiotensin and bradykinin peptides in 6-week-old male homozygous TGR(mRen-2)27 rats. Systolic blood pressure of TGR(mRen-2)27 rats was 212 +/- 4 mm Hg (mean +/- SEM, n = 25) compared with 108 +/- 2 mm Hg (n = 29) for age- and sex-matched Sprague-Dawley rats. Compared with control rats, TGR(mRen-2)27 rats had increased plasma levels of active renin (4.5-fold), prorenin (300-fold), and Ang II (fourfold) as well as tissue levels of Ang II (twofold to fourfold in kidney, adrenal, heart, aorta, brown adipose tissue, and lung and 18-fold in brain). Plasma angiotensinogen levels were reduced to 73% of control, and plasma aldosterone levels were increased fourfold. Plasma angiotensin-converting enzyme was reduced to 64% of control. Compared with control rats, TGR(mRen-2)27 rats had increased bradykinin levels in brown adipose tissue (1.9-fold) and lung (1.6-fold).(ABSTRACT TRUNCATED AT 250 WORDS)
转基因TGR（mRen-2）27大鼠是将Ren-2小鼠肾素基因转染到斯普拉格-道利大鼠基因组中构建而成的，这种大鼠在年轻时就会出现严重高血压，对血管紧张素转换酶抑制剂和1型血管紧张素II（Ang II）受体拮抗剂有反应。尽管有证据表明这种高血压依赖于Ang II，但TGR（mRen-2）27大鼠的肾素和肾素mRNA含量受到抑制，并且这些大鼠的肾素和Ang II血浆水平存在争议。我们研究了转基因对6周龄雄性纯合TGR（mRen-2）27大鼠循环和组织中血管紧张素和缓激肽肽水平的影响。TGR（mRen-2）27大鼠的收缩压为212±4 mmHg（平均值±标准误，n = 25），而年龄和性别匹配的斯普拉格-道利大鼠的收缩压为108±2 mmHg（n = 29）。与对照大鼠相比，TGR（mRen-2）27大鼠的活性肾素（4.5倍）、肾素原（300倍）和Ang II（4倍）血浆水平升高，以及Ang II组织水平升高（在肾脏、肾上腺、心脏、主动脉、棕色脂肪组织和肺中为2倍至4倍，在脑中为18倍）。血浆血管紧张素原水平降至对照的73%，血浆醛固酮水平升高4倍。血浆血管紧张素转换酶降至对照的64%。与对照大鼠相比，TGR（mRen-2）27大鼠棕色脂肪组织（1.9倍）和肺（1.6倍）中的缓激肽水平升高。（摘要截断于250字）
