Hypertension, Vol 19, 692-696, Copyright © 1992 by American Heart Association
K Yamamoto, MC Chappell, KB Brosnihan and CM Ferrario
We investigated the processing enzymes involved in the formation of
circulating angiotensin-(1-7) after intravenous administration of
angiotensin I to conscious spontaneously hypertensive and Wistar-Kyoto
rats. Immunoreactive products, including angiotensin I, angiotensin II, and
angiotensin-(1-7), were measured in arterial blood by three specific
radioimmunoassays. Angiotensin I infusion (2 nmol) induced a rapid increase
in immunoreactive angiotensin II and angiotensin-(1-7). Pretreatment with
the angiotensin converting enzyme inhibitor enalaprilat (2 mg/kg)
eliminated angiotensin II formation and augmented circulating levels of
angiotensin I and angiotensin-(1-7) in spontaneously hypertensive and
Wistar-Kyoto rats. The elevated levels of angiotensin-(1-7) in
enalaprilat-treated rats were blocked by concurrent treatment with the
neutral endopeptidase (EC 3.4.24.11) inhibitor SCH 39,370 (15 mg/kg) in
both strains. Administration of SCH 39,370 alone decreased
angiotensin-(1-7) levels in spontaneously hypertensive rats, whereas
angiotensin II levels increased in both strains (p less than 0.01).
Comparisons of the metabolism of angiotensin I in the two rat strains
showed increased formation of angiotensin-(1-7) in spontaneously
hypertensive rats not given any of the enzyme inhibitors. In addition,
levels of angiotensin I were higher after administration of SCH 39,370 in
hypertensive rats. These novel findings reveal that neutral endopeptidase
EC 3.4.24.11 participates in the conversion of angiotensin I to
angiotensin-(1-7) and in the metabolism of angiotensin II in the
circulation of both spontaneously hypertensive and Wistar-Kyoto rats. Our
results suggest that neutral endopeptidase EC 3.4.24.11 is a major
enzymatic constituent of the circulating renin-angiotensin system.
ARTICLES
In vivo metabolism of angiotensin I by neutral endopeptidase (EC 3.4.24.11) in spontaneously hypertensive rats
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Cleveland, Ohio 44195-5286.
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