ANGIOTENSIN(1-7) IN THE SPONTANEOUSLY HYPERTENSIVE RAT

We profiled the concentrations of angiotensin I (Ang I), angiotensin I I (Ang 11), and angiotensin(1-7) [Ang(1-7)] by the combination of radi oimmunoassay and high performance liquid chromatography in the blood o f 14-week-old male Wistar-Kyoto (WKY) and spontaneously hypertensive r ats (SHR) drinking either tap water or a solution containing ceranapri l (30 mg/kg) or lisinopril (20 mg/kg) for 14 days. Differences in the chemical and pharmacokinetic properties of the two converting enzyme i nhibitors ruled out class-related effects. Plasma renin activity, angi otensin converting enzyme (ACE) activity, and plasma levels of Ang I a nd Ang II were the same in vehicle-treated WKY and SHR. In contrast, p lasma 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 enzy me inhibition reduced the blood pressure of WKY and SHR, and augmented their intake of water and output of urine. These changes were associa ted with increases in renin activity and plasma levels of Ang I and An g(1-7). In both WKY and SHR, lisinopril had a greater effect in inhibi ting plasma and cerebrospinal fluid ACE, reducing levels of plasma ang iotensinogen, and increasing the concentrations of authentic Ang II. T he principal finding of this study is that plasma Ang(1-7) is the sole component of the circulating angiotensin system that is elevated in t he established phase of genetic hypertension. The finding that chronic inhibition of ACE augments circulating levels of Ang(1-7) evidenced t he existence of functional pathways for the alternate processing of An g I.