Angiotensin(1-7) in the spontaneously hypertensive rat.
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.
Kohara
K
K
Hypertension Center, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1095.
Brosnihan
K B
KB
Ferrario
C M
CM
D000803:Angiotensin I; D000804:Angiotensin II / Q000097:blood*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000097:blood* / Q000503:physiopathology; D017706:Lisinopril / Q000494:pharmacology; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010446:Peptide Fragments / Q000097:blood*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012083:Renin / Q000097:blood; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D009943:Organophosphorus Compounds; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; D011392:Proline; D017706:Lisinopril; D012083:Renin; C118790:angiotensin I (1-7); C054518:ceronapril