Characterization of endothelin receptors in human varicose veins

D. A. Barber, X. Wang, P. Gloviczki, V. M. Miller

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Purpose: Experiments were designed to characterize endothelin receptors in human varicose veins. Three groups of veins were studied: (1) varicose vein (VV) tributaries of the greater saphenous vein from patients who were undergoing vein stripping for primary varicosity; (2) greater saphenous veins (SVs) from the same patients; and (3) greater saphenous veins from patients without varicosity who were undergoing arterial reconstruction (control). Methods: Veins were either cut into rings and suspended in organ chambers for measurement of isometric force, prepared for receptor binding of membrane proteins, or were prepared for measurement of preproendothelin mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Endothelin- 1 (10-11 to 10-7 mol/L) produced similar concentration- dependent contractions in rings with or without endothelium. Maximal tensions were significantly greater in control veins compared with either SVs or VVs. Sarafotoxin S6c (10-11 to 3 x 10-7 mol/L), which is selective for the endothelin-B receptor, also produced concentration-dependent increases in tension in all veins. Sarafotoxin S6c responses in VVs were shifted significantly rightward compared with either SVs or control. Maximal tensions to sarafotoxin S6c also were significantly greater in control veins compared with either SVs or VVs. In receptor binding studies, the number of binding sites as defined by competitive inhibition of 125I-endothelin-1 by endothelin-1 was less in VVs than control veins. Competitive inhibition of 125I-endothelin-1 with endothelin-3 (both A and B receptors) or sarafotoxin S6c (B receptors only) suggests that the difference in receptor number between varicose and nonvaricose veins is attributable to differences in the endothelin-B receptor subtype. Binding affinities were not significantly different for either of the receptor subtypes in all veins studied. Preproendothelin mRNA as quantitated by RT-PCR tended to be higher in VVs compared with either SVs or control veins. Conclusions: Decreased contractions to endothelin-1 in both varicose and saphenous veins of patients with primary varicosity may be associated with a decrease in the number of receptors. These receptors may be downregulated in response to increased production of endothelin-1, which is regulated at the transcriptional level.

Original languageEnglish (US)
Pages (from-to)61-69
Number of pages9
JournalJournal of vascular surgery
Issue number1
StatePublished - 1997

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine


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