Radioimmunoassay evidence that the pressor effect of big endothelin-1 is due to local conversion to endothelin-1

Biochem Pharmacol. 1995 Jan 31;49(3):375-80. doi: 10.1016/0006-2952(94)00425-l.

Abstract

Compared with endothelin-1 (ET-1), big endothelin-1 (big ET-1) is only weakly active on isolated vascular smooth muscle preparations. However, on systemic administration high doses of big ET-1 (1 nmol.kg-1) are approximately equipotent to ET-1, indicating the existence of an endothelin converting enzyme in the circulation that rapidly converts big ET-1 to ET-1. In this study arterial blood levels of big ET-1 and ET-1 immunoreactivity were measured after bolus i.v. administration of big ET-1 (1 or 3 nmol.kg-1) or ET-1 (1 nmol.kg-1) in anaesthetised male Wistar rats. In addition, the effect of phosphoramidon (10 mg.kg-1) on the pressor response to big ET-1 and its disappearance rate from the circulation were examined. After big ET-1 injection, circulating ET-1 concentrations did not exceed 2% of the big ET-1 level. Phosphoramidon reduced the pressor response to big ET-1 by 93%, but did not alter its rate of clearance from the circulation. Thus exogenous big ET-1 is converted locally in the vasculature and its disappearance from the circulation is not dependent on conversion to ET-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Chromatography, High Pressure Liquid
  • Endothelin-1
  • Endothelins / blood*
  • Endothelins / pharmacokinetics
  • Endothelins / pharmacology*
  • Glycopeptides / pharmacology
  • Male
  • Protein Precursors / blood*
  • Protein Precursors / pharmacokinetics
  • Protein Precursors / pharmacology*
  • Radioimmunoassay
  • Rats
  • Rats, Wistar

Substances

  • Endothelin-1
  • Endothelins
  • Glycopeptides
  • Protein Precursors
  • phosphoramidon