Metabolism of Big endothelin-1 (1-38) and (22-38) in the human circulation in relation to production of endothelin-1 (1-21).
Healthy male volunteers received intravenous infusions of Big endothelin (ET)-1 (1-38) or Big ET-1 (22-38). Blood samples were drawn from catheters in the brachial and pulmonary arteries and the hepatic, renal, jugular and deep forearm veins. The in vivo half-lives of circulating plasma Big ET-1 (1-38) were 6.6 +/- 0.3 min for the initial phase and 23 +/- 1.4 min for the late phase. The corresponding half-lives of Big ET-1 (22-38) were considerably shorter, being 0.9 +/- 0.03 min (P < 0.01) and 3.1 +/- 0.4 min (P < 0.01), respectively. This was concordant with the efficient regional clearance of Big ET-1 (22-38), which was most prominent in the forearm muscle (51 +/- 3%), liver (44 +/- 5%) and kidney (43 +/- 3%) and less pronounced in the lungs (14 +/- 2%) and brain (22 +/- 5%). Significant fractional extraction of Big ET-1 (1-38) was only found for the liver (30 +/- 2%) and kidney (44 +/- 3%). During the infusion of Big ET-1 (1-38) a positive veno-arterial gradient of ET-1-LI was noted only for the kidney, indicating production of ET-1. In conclusion, whereas Big ET-1 (22-38) is eliminated in skeletal muscle, splanchnic, renal, pulmonary and cerebral vascular beds, Big ET-1 (1-38) is extracted mainly in the renal and splanchnic vasculature. Furthermore, plasma half-life of Big ET-1 (1-38) is much longer than that of both ET-1 and Big ET-1 (22-38) in man. Thus, for investigation of the secretory activity of the ET-1-system measurements of Big ET-1 (1-38) levels may be a better approach.
Hemsén
A
A
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Ahlborg
G
G
Ottosson-Seeberger
A
A
Lundberg
J M
JM
D000328:Adult; D019332:Endothelin-1; D016232:Endothelins / Q000096:biosynthesis* / Q000097:blood*; D006207:Half-Life; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D011498:Protein Precursors / Q000097:blood*; D011863:Radioimmunoassay
D019332:Endothelin-1; D016232:Endothelins; D010446:Peptide Fragments; D011498:Protein Precursors