1. Academic Validation
  2. Metabolism of Big endothelin-1 (1-38) and (22-38) in the human circulation in relation to production of endothelin-1 (1-21)

Metabolism of Big endothelin-1 (1-38) and (22-38) in the human circulation in relation to production of endothelin-1 (1-21)

  • Regul Pept. 1995 Feb 14;55(3):287-97. doi: 10.1016/0167-0115(94)00119-i.
A Hemsén 1 G Ahlborg A Ottosson-Seeberger J M Lundberg
Affiliations

Affiliation

  • 1 Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Abstract

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.

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