Plasma endothelin and renal endothelin are two distinct systems involved in volume homeostasis

This study of seven healthy young subjects was designed both to establish whether endothelin-1 (ET- 1) is involved in the homeostasis of blood volume and to clarify the relationship between plasma and urinary ET-l. Acute volume expansion (+ 17%) caused increases in venous blood pressure (+4.4 mmHg) and the plasma concentration of ET-l (+ 129%) and a decrease (-99%) in the urinary excretion of ET-l. Volume depletion (-8.5%) provoked an increase in the plasma concentration of ET-1 without altering the urinary excretion of ET-l. Passive elevation of an arm resulting in a local decrease of venous blood pressure ( - 17 mmHg) elicited an increase of the local formation of ET-l, with a lo-fold increase in the venousarterial gradient compared with the opposite arm, which lay at the level of the heart. The increased local formation of ET-l was blunted by volume expansion. The results indicate that 1) plasma ET-1 and urinary ET-1 represent two different endothelin- generating systems, both of which are involved in the regulation of blood volume, and 2) plasma ET-l appears to be an important mechanism for the long-lasting adaptations of venous wall tension to changes in blood volume.