BINDING OF ENDOTHELIN TO PLASMA-PROTEINS AND TISSUE RECEPTORS - EFFECTS ON ENDOTHELIN DETERMINATION, VASOACTIVITY, AND TISSUE KINETICS

In vitro binding of (3-[I-125]Tyr)-endothelin-1 ([I-125]ET-1) and (3-[I-125]Tyr)-big ET-1(1-38) ([I-125]big ET-1) to plasma proteins of healthy humans, cardiac patients and normotensive and hypertensive rats was investigated by equilibrium dialysis. Binding of both tracers was similar in plasma from healthy humans, patients with congestive heart failure, and following myocardial infarction (similar to 60%), and marginally higher in rat plasmas (similar to 70%). Binding of [I-125]ET-1 to human plasma could be explained by binding to human serum albumin. Endogenous plasma ET-1 levels were similar to 9 pg/ml in healthy humans, and similar to 12-16 pg/ml in cardiac patients; big ET-1 concentrations were approximately two- to threefold higher. ET-1 bound to plasma protein was partly lost in column extraction. In rat isolated perfused hearts, the coronary dilator and constrictor potency of exogenous free and albumin-bound ET-1 was similar, whereas the kinetics of endogenous ET-1 was impeded by tight binding to ET receptors. The data indicate that binding of ET-1 to plasma proteins is without effect on peptide vasoactivity, but binding to tissue receptors greatly impedes its tissue kinetics.