Inhibition of tissue angiotensin converting enzyme. Quantitation by autoradiography

Journal Article · Tue Mar 01 04:00:00 EST 1988 · Hypertension (Dallas); (United States)

DOI:https://doi.org/10.1161/01.HYP.11.3.230· OSTI ID:7000117

Sakaguchi, K; Chai, S Y; Jackson, B; Johnston, C I; Mendelsohn, F A

Inhibition of angiotensin converting enzyme (ACE) in serum and tissues of rats was studied after administration of lisinopril, an ACE inhibitor. Tissue ACE was assessed by quantitative in vitro autoradiography using the ACE inhibitor (/sup 125/I)351A, as a ligand, and serum ACE was measured by a fluorimetric method. Following oral administration of lisinopril (10 mg/kg), serum ACE activity was acutely reduced but recovered gradually over 24 hours. Four hours after lisinopril administration, ACE activity was markedly inhibited in kidney (11% of control level), adrenal (8%), duodenum (8%), and lung (33%; p less than 0.05). In contrast, ACE in testis was little altered by lisinopril (96%). In brain, ACE activity was markedly reduced 4 hours after lisinopril administration in the circumventricular organs, including the subfornical organ (16-22%) and organum vasculosum of the lamina terminalis (7%; p less than 0.05). In other areas of the brain, including the choroid plexus and caudate putamen, ACE activity was unchanged. Twenty-four hours after administration, ACE activity in peripheral tissues and the circumventricular organs of the brain had only partially recovered toward control levels, as it was still below 50% of control activity levels. These results establish that lisinopril has differential effects on inhibiting ACE in different tissues and suggest that the prolonged tissue ACE inhibition after a single oral dose of lisinopril may reflect targets involved in the hypotensive action of ACE inhibitors.

• Research Organization: Univ. of Melbourne, Victoria (Australia)
• OSTI ID: 7000117
• Journal Information: Hypertension (Dallas); (United States), Journal Name: Hypertension (Dallas); (United States) Vol. 11:3; ISSN HPRTD
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADRENAL GLANDS
ANGIOTENSIN
ANIMALS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENDOCRINE GLANDS
ENZYME ACTIVITY
ENZYME INHIBITORS
ENZYMES
GASTROINTESTINAL TRACT
GLANDS
GLOBULINS
GONADS
HYDROLASES
INTERMEDIATE MASS NUCLEI
INTESTINES
IODINE 125
IODINE ISOTOPES
ISOTOPES
KIDNEYS
KINETICS
LUNGS
MALE GENITALS
MAMMALS
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORAL ADMINISTRATION
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HYDROLASES
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RESPIRATORY SYSTEM
RODENTS
SMALL INTESTINE
TESTES
VASOCONSTRICTORS
VERTEBRATES