Kohara K, Brosnihan K B, Ferrario C M
Hypertension Center, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1095.
Peptides. 1993 Sep-Oct;14(5):883-91. doi: 10.1016/0196-9781(93)90063-m.
We profiled the concentrations of angiotensin I (Ang I), angiotensin II (Ang II), and angiotensin(1-7) [Ang(1-7)] by the combination of radioimmunoassay and high performance liquid chromatography in the blood of 14-week-old male Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) drinking either tap water or a solution containing ceranapril (30 mg/kg) or lisinopril (20 mg/kg) for 14 days. Differences in the chemical and pharmacokinetic properties of the two converting enzyme inhibitors ruled out class-related effects. Plasma renin activity, angiotensin converting enzyme (ACE) activity, and plasma levels of Ang I and Ang II were the same in vehicle-treated WKY and SHR. In contrast, plasma levels of both Ang(1-7) and vasopressin in SHR were 3.7-fold and 2.6-fold higher, respectively (p < 0.05). Angiotensin converting enzyme inhibition reduced the blood pressure of WKY and SHR, and augmented their intake of water and output of urine. These changes were associated with increases in renin activity and plasma levels of Ang I and Ang(1-7). In both WKY and SHR, lisinopril had a greater effect in inhibiting plasma and cerebrospinal fluid ACE, reducing levels of plasma angiotensinogen, and increasing the concentrations of authentic Ang II. The principal finding of this study is that plasma Ang(1-7) is the sole component of the circulating angiotensin system that is elevated in the established phase of genetic hypertension. The finding that chronic inhibition of ACE augments circulating levels of Ang(1-7) evidenced the existence of functional pathways for the alternate processing of Ang I.
我们通过放射免疫测定法和高效液相色谱法联用，对饮用自来水或含西拉普利（30毫克/千克）或赖诺普利（20毫克/千克）溶液14天的14周龄雄性Wistar-Kyoto（WKY）大鼠和自发性高血压大鼠（SHR）血液中的血管紧张素I（Ang I）、血管紧张素II（Ang II）和血管紧张素（1-7）[Ang(1-7)]浓度进行了分析。两种转化酶抑制剂在化学和药代动力学特性上的差异排除了类相关效应。在给予赋形剂处理的WKY大鼠和SHR大鼠中，血浆肾素活性、血管紧张素转化酶（ACE）活性以及Ang I和Ang II的血浆水平相同。相比之下，SHR大鼠中Ang(1-7)和血管加压素的血浆水平分别高出3.7倍和2.6倍（p<0.05）。血管紧张素转化酶抑制降低了WKY大鼠和SHR大鼠的血压，并增加了它们的饮水量和尿量。这些变化与肾素活性以及Ang I和Ang(1-7)血浆水平的升高有关。在WKY大鼠和SHR大鼠中，赖诺普利在抑制血浆和脑脊液ACE、降低血浆血管紧张素原水平以及增加天然Ang II浓度方面具有更大的作用。本研究的主要发现是，血浆Ang(1-7)是循环血管紧张素系统中在遗传性高血压确立阶段升高的唯一成分。慢性抑制ACE可增加循环中Ang(1-7)水平这一发现证明了存在Ang I替代加工的功能途径。
