Experiments were designed to characterize endothelin receptors in canine femoral veins and to determine whether their distribution or sensitivity could be altered by chronic changes in blood flow and oxygen tension in veins proximal to an arteriovenous fistula. Endothelium was removed from unoperated or fistula-operated femoral veins of anesthetized dogs. Veins were cut into rings and suspended in organ chambers for the measurement of isometric force or frozen for isolation of membrane proteins. Endothelin-1, endothelin-3, and sarafotoxin S6c caused concentration-dependent increases in tension in all rings. In rings of unoperated veins, maximal tensions were significantly less to endothelin-3 and sarafotoxin S6c than to endothelin-1. In rings of fistula-operated veins, maximal tensions to endothelin-1 and endothelin-3 were the same. Contractions to endothelin-1 or endothelin-3 in unoperated veins were not inhibited by an antagonist of endothelin-A receptors, BQ-123. Binding of 125I-labeled endothelin-1 (125I-endothelin-1) to membranes from veins without endothelium increased as a function of membrane protein. Affinity of receptors, as determined by competitive inhibition of 125I- endothelin-1 was as follows: endothelin-1 > endothelin-3 > sarafotoxin S6c. Competitive inhibition of 125I-endothelin-1 by endothelin-3 and sarafotoxin S6c was significant for a two-site binding model in all veins. The total number of binding sites was reduced significantly in fistula- operated veins; the relative proportions of high- and low-affinity binding sites did not change. Affinity of high- and low-affinity receptors increased in fistula-operated veins. These results indicate that at least two subtypes of endothelin receptors initiate contraction of smooth muscle of canine femoral veins. Expression and affinity of these receptors can be altered by chronic exposure of the veins to increases in blood flow and oxygen tension.
|Original language||English (US)|
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|Issue number||1 37-1|
|State||Published - Jan 1 1995|
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)