Ocaranza María Paz, Palomera Cristián, Román Maritza, Bargetto Jorge, Lavandero Sergio, Jalil Jorge E
Department of Cardiovascular Diseases, Medical School, P. Catholic University of Chile, Santiago, Chile.
Life Sci. 2006 Feb 28;78(14):1535-42. doi: 10.1016/j.lfs.2005.07.026. Epub 2005 Oct 17.
To determine circulating angiotensin-(1-7) [Ang-(1,7)] levels in rats with different angiotensin converting enzyme (ACE) genotypes and to evaluate the effect of hypertension on levels of this heptapeptide, plasma levels of angiotensin II (Ang II) and Ang-(1-7) were determined by HPLC and radioimmunoassay in (a) normotensive F0 and F2 homozygous Brown Norway (BN; with high ACE) or Lewis (with low ACE) rats and (b) in hypertensive F2 homozygous male rats (Goldblatt model). Genotypes were characterized by PCR and plasma ACE activity measured by fluorimetry. Plasma ACE activity was 2-fold higher (p < 0.05) in homozygous BN compared to homozygous Lewis groups. In the Goldblatt groups, a similar degree of hypertension and left ventricular hypertrophy was observed in rats with both genotypes. Plasma Ang II levels were between 300-400% higher (p < 0.05) in the BN than in the Lewis rats, without increment in the hypertensive animals. Plasma Ang-(1-7) levels were 75-87% lower in the BN rats (p < 0.05) and they were significantly higher (p < 0.05) in the hypertensive rats from both genotypes. Plasma levels of Ang II and Ang-(1-7) levels were inversely correlated in the normotensive rats (r = -0.64; p < 0.001), but not in the hypertensive animals. We conclude that there is an inverse relationship between circulating levels of Ang II and Ang-(1-7) in rats determined by the ACE gene polymorphism. This inverse relation is due to genetically determined higher ACE activity. Besides, plasma levels of Ang-(1-7) increase in renovascular hypertension.
为了测定不同血管紧张素转换酶（ACE）基因型大鼠的循环血管紧张素-（1-7）[Ang-（1,7）]水平，并评估高血压对这种七肽水平的影响，通过高效液相色谱法（HPLC）和放射免疫分析法测定了（a）正常血压的F0和F2纯合子棕色挪威大鼠（BN；ACE活性高）或Lewis大鼠（ACE活性低）以及（b）高血压F2纯合子雄性大鼠（Goldblatt模型）的血浆血管紧张素II（Ang II）和Ang-（1-7）水平。通过聚合酶链反应（PCR）鉴定基因型，并用荧光法测定血浆ACE活性。与纯合子Lewis组相比，纯合子BN组的血浆ACE活性高2倍（p<0.05）。在Goldblatt组中，两种基因型的大鼠均观察到相似程度的高血压和左心室肥厚。BN大鼠的血浆Ang II水平比Lewis大鼠高300 - 400%（p<0.05），高血压动物中未增加。BN大鼠的血浆Ang-（1-7）水平低75 - 87%（p<0.05），两种基因型的高血压大鼠中该水平显著更高（p<0.05）。在正常血压大鼠中，血浆Ang II和Ang-（1-7）水平呈负相关（r = -0.64；p<0.001），但在高血压动物中无此相关性。我们得出结论，由ACE基因多态性决定的大鼠循环中Ang II和Ang-（1-7）水平之间存在负相关关系。这种负相关是由于基因决定的较高ACE活性所致。此外，肾血管性高血压时血浆Ang-（1-7）水平升高。
