Hilgers K F, Veelken R, Mai M, Ganten U, Ganten D, Luft F C, Mann J F
Department of Medicine-Nephrology, University of Erlangen-Nuremberg, Germany.
J Hypertens. 1993 Oct;11(10):1053-9. doi: 10.1097/00004872-199310000-00008.
Linkage studies have shown that the gene locus for angiotensin converting enzyme (ACE) is associated with the expression of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). We tested the hypothesis that the conversion of angiotensin I (Ang I) to angiotensin II (Ang II) in blood vessels is elevated in SHRSP.
We measured the conversion rate of Ang I to Ang II during one pass through an isolated resistance vessel bed. We used the same substrains of SHRSP and Wistar-Kyoto control rats (WKY) that had been employed in the earlier linkage studies.
Isolated hindquarters from young and adult (10- to 12- and 36- to 38-week-old) rats were perfused with an artificial medium and then infused with Ang I at 0.5 and 2 pmol/ml. Ang I and II were measured with high-performance liquid chromatography and radioimmunoassay in hindquarter effluent and in blank control channels. Conversion and extraction rates were calculated from angiotensin levels in hindquarter and blank perfusion channels, respectively.
The conversion rates of Ang I to Ang II did not differ between SHRSP and WKY in young or in adult rats. Captopril completely abolished the formation of Ang II in all groups of rats. During infusion at the higher dose of Ang I, the extraction of Ang I was significantly decreased in SHRSP compared with WKY.
Our results are consistent with the notion that the metabolism of angiotensin is decreased in spontaneously hypertensive rats. However, we found no support for the hypothesis that vascular ACE is responsible for high blood pressure in SHRSP. These findings suggest that other genes close to the ACE locus or the hyperexpression of the enzyme in other areas may contribute to hypertension in these rats.
连锁研究表明，血管紧张素转换酶（ACE）基因位点与易中风自发性高血压大鼠（SHRSP）的高血压表达相关。我们检验了如下假设：SHRSP血管中血管紧张素I（Ang I）向血管紧张素II（Ang II）的转化升高。
我们测量了Ang I单次通过分离的阻力血管床期间向Ang II的转化率。我们使用了与早期连锁研究中相同的SHRSP和Wistar-Kyoto对照大鼠（WKY）亚系。
用人工培养基灌注年轻和成年（10至12周龄和36至38周龄）大鼠分离的后肢，然后以0.5和2 pmol/ml的浓度注入Ang I。用高效液相色谱法和放射免疫分析法测量后肢流出液和空白对照通道中的Ang I和II。转化率和提取率分别根据后肢灌注通道和空白灌注通道中的血管紧张素水平计算得出。
年轻或成年大鼠中，SHRSP和WKY之间Ang I向Ang II的转化率没有差异。卡托普利完全消除了所有大鼠组中Ang II的形成。在以较高剂量的Ang I进行灌注期间，与WKY相比，SHRSP中Ang I的提取显著降低。
我们的结果与自发性高血压大鼠血管紧张素代谢降低的观点一致。然而，我们没有找到支持血管ACE导致SHRSP高血压这一假设的证据。这些发现表明，靠近ACE基因位点的其他基因或该酶在其他区域的过度表达可能导致这些大鼠的高血压。
