The effects of N-[8-amino-1(S)-carboxyoctyl]-
L-alanyl-L-proline (AB-47, CAS 120008-53-9), an orally active
angiotensin converting enzyme inhibitor, on the central nervous, respiratory and cardiovascular, autonomic systems, isolated smooth muscles and other functions were investigated in various experimental animals.
AB-47 had no effect on central nervous, autonomic systems and isolated smooth muscles.
AB-47 (10 and 30 micrograms/kg i.v.) significantly lowered femoral blood pressure without affecting respiration and heart rate in anesthetized rats. However,
AB-47 had no effect on the contractile tension of mammalian isolated atrium and aorta.
AB-47 had no effect on gastrointestinal transit in mice. Very slight injury of gastric mucosa was observed 4 h after the
oral administration of
AB-47 in rats but
AB-47 did not damage the small intestinal mucosa.
AB-47 had no effect on the contraction of rat phrenic nerve-diaphragm preparation induced by electrical stimulation.
AB-47 did not affect the incidence of
acetic acid-induces writhings.
AB-47 potentiated
carrageenan-induced hind paw
edema in rats. The potentiation of
edema may be due to an accumulation of
bradykinin induced by the inhibition of
angiotensin converting enzyme (ACE), because ACE is the identical
enzyme with
kinase II. The pretreatment of
AB-47 for 7 days (1, 3, 10 mg/kg/d p.o.) inhibited the
cardiac hypertrophy induced by
isoproterenol (
isoprenaline). This result suggests that the renin-angiotensin-aldosterone system directly or indirectly participates in the
cardiac hypertrophy induced by
isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)