Pharmacokinetics and distribution of heparin-binding growth factor I (endothelial cell growth factor) in the rat

Journal Article · Wed Feb 01 04:00:00 EST 1989 · Circ. Res.; (United States)

DOI:https://doi.org/10.1161/01.RES.64.2.227· OSTI ID:6470477

Rosengart, T K; Kuperschmid, J P; Maciag, T; Clark, R E

Heparin-binding growth factor I (HBGF I), previously designated as endothelial cell growth factor, is a potent mitogen for endothelial cells in vitro, which may prove useful for promoting endothelial regeneration in vivo. Analysis of the pharmacokinetics and organ distribution of HBGF I is necessary before use of HBGF I as a pharmacological agent. Consequently, pharmacological studies were carried out with (125I)HBGF I in the rat. Intravenous injections of HBGF I were given with or without heparin (2.5 units/ng HBGF I). Blood concentrations of HBGF I decreased by one half 17 seconds after HBGF I bolus. This time was prolonged to 60 seconds when HBGF I was injected with heparin. The elimination half-life of HBGF I was 14 minutes in the presence of heparin. The highest concentrations of HBGF I following intravenous bolus were found in kidney, liver, and spleen, and the lowest in fat and brain. Heparin increased HBGF I concentrations in blood and all organs measured except kidney, which was significantly decreased (p less than 0.01). Intact HBGF I was recoverable from blood 5 minutes following intravenous administration. HBGF I underwent near-complete proteolytic digestion after more prolonged ex vivo incubation with rat plasma, but HBGF I was protected from proteolysis when incubations were conducted in the presence of heparin. Thus, it is feasible that HBGF I can be administered as a pharmacological agent in the presence of heparin. Further studies assessing acceleration of in vivo endothelial growth using HBGF I with heparin appear warranted.

• Research Organization: National Heart, Lung, and Blood Institute, Bethesda, MD (USA)
• OSTI ID: 6470477
• Journal Information: Circ. Res.; (United States), Journal Name: Circ. Res.; (United States) Vol. 64:2; ISSN CIRUA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMAL TISSUES
ANIMALS
ANTICOAGULANTS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
BODY
CARBOHYDRATES
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENDOTHELIUM
GROWTH FACTORS
HEMATOLOGIC AGENTS
HEPARIN
INJECTION
INTAKE
INTERMEDIATE MASS NUCLEI
INTRAVENOUS INJECTION
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MITOGENS
MUCOPOLYSACCHARIDES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
POLYSACCHARIDES
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RODENTS
SACCHARIDES
TISSUE DISTRIBUTION
TISSUES
TRACER TECHNIQUES
VERTEBRATES