Elimination of intravenously injected endothelin-1 from the circulation of the rat

Journal Article · Sun Jan 01 04:00:00 EST 1989 · J. Cardiovasc. Pharmacol.; (United States)

DOI:https://doi.org/10.1097/00005344-198900135-00024· OSTI ID:5702077

Shiba, R; Yanagisawa, M; Miyauchi, T; Ishii, Y; Kimura, S; Uchiyama, Y; Masaki, T; Goto, K

The rate of elimination and the fate of endothelin-1 (ET-1) from the circulating blood was studied in urethane-anesthetized rats by intravenous injection of (125I)-labeled ET-1. The vasoconstrictor activities of the iodinated ET-1 were confirmed to be similar to those of native ET-1. Following i.v. bolus injection of 30 pmol/kg of (125I)-ET-1 into the femoral vein, the total radioactivity of the right atrial blood decayed rapidly, with a half-life of 7 min. At 5 min after the injection, the administered radioactivity distributed chiefly to the parenchyma of the lungs, kidneys, and liver. The analysis of the chemical form of labeled peptides from the plasma by reverse-phase high-performance liquid chromatography (HPLC) demonstrated no appreciable amount of degraded forms of (125I)-ET-1 in the blood for up to 60 min. (125I)-ET-1 was also stable for up to 60 min upon incubation in vitro with heparinized rat blood at 37 degrees C. Even when the same amount of labeled ET-1 was injected together with a pressor dose (1,500 pmol/kg) of cold ET-1, the half-life of the radioactivity in the bloodstream was exactly identical to that for (125I)-ET-1 alone. Nevertheless, the pressor response continued for more than 90 min after i.v. bolus injection of 1500 pmol/kg of ET-1 to the rat. These results clearly indicate that the elimination of ET-1 from circulating blood and the ET-1-induced pressor response are not in parallel, and the relatively rapid disappearance of ET-1 from the bloodstream is mostly due to the removal of the peptide by the parenchymal tissues, in the anesthetized rat. The long-lasting pressor action of ET-1 may be ascribed to our previous finding that the dissociation of ET-1 from its specific binding sites on vascular smooth muscle cells is extremely slow.

• Research Organization: Univ. of Tsukuba (Japan)
• OSTI ID: 5702077
• Journal Information: J. Cardiovasc. Pharmacol.; (United States), Journal Name: J. Cardiovasc. Pharmacol.; (United States) Vol. 13 Suppl 5; ISSN JCPCD
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL HALF-LIFE
BLOOD PRESSURE
BLOOD-PLASMA CLEARANCE
CARDIOVASCULAR AGENTS
CHROMATOGRAPHY
CLEARANCE
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
INJECTION
INTAKE
INTERMEDIATE MASS NUCLEI
INTRAVENOUS INJECTION
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MEMBRANE PROTEINS
METABOLISM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDES
PROTEINS
RADIOISOTOPES
RATS
RECEPTORS
RODENTS
SEPARATION PROCESSES
TISSUE DISTRIBUTION
TRACER TECHNIQUES
VASOCONSTRICTORS
VERTEBRATES