/sup 3/H-Benzoyl-Ala-Gly-Pro: a new synthetic substrate of pulmonary endothelial angiotensin converting enzyme in vivo

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5450401

Catravas, J D; Ryan, J W

The authors have investigated the metabolism of /sup 3/H-Benzoyl-Ala-Gly-Pro (BAGP) by pulmonary angiotensin converting enzyme (ACE) in anesthetized rabbits utilizing indicator dilution techniques under first order reaction conditions. Arterial outflow curves of /sup 3/H and /sup 14/C-dextran were congruent, and indicator mean transit times were identical, indicating that both parent and product remained within the vascular spaces during a single transpulmonary passage. At normal pulmonary plasma flow (252 +/- 19) ml/min) single pass metabolism of /sup 3/H-BAGP averaged 59 +/- 3% (N = 5) and the Amax/Km ratio was 225 +/- 14 ml/min. When plasma flow was raised to 360 +/- 46 ml/min substrate metabolism was slightly but significantly reduced to 54 +/- 3%. Amax/Km, however, rose to 308 +/- 29 ml/min (p < 0.05) suggesting increased enzyme mass due to microvascular recruitment. The in vivo transpulmonary metabolism of /sup 3/H-BAGP is considerably less than that of the other commonly utilized substrate /sup 3/H-BPAP (80-90% conversion), agreeing with in vitro estimations of Kc/Km ratios for the two compounds (BAGP: 2.4 x 10/sup 7/, BPAP: 4.8 x 10/sup 7/ M/sup -1/ . sec/sup -1/). The use of /sup 3/H-BAGP as an AE substrate in vivo may prove advantageous when substantial alterations in pulmonary ACE activity are anticipated due to pathophysiological interventions.

• Research Organization: Medical College of Georgia, Augusta
• OSTI ID: 5450401
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANGIOTENSIN
ANIMAL TISSUES
BLOOD FLOW
BODY
CARBON 14 COMPOUNDS
CARDIOVASCULAR AGENTS
DRUGS
ENDOTHELIUM
GLOBULINS
IN VIVO
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LUNGS
METABOLISM
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RESPIRATORY SYSTEM
SUBSTRATES
TISSUES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASOCONSTRICTORS