Chronic increases in blood flow upregulate endothelin-B receptors in arterial smooth muscle

Dustan A. Barber, Sandra R. Michener, Steven C. Ziesmer, Virginia M. Miller

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Experiments were designed to characterize endothelin receptors in arteries after chronic increases in blood flow. A fistula was created between the femoral artery and vein in one hindlimb of dogs; contralateral blood vessels were sham operated. Sham- and fistula-operated arteries were removed 6 wk postoperatively. Some arteries were prepared for measurement of isometric force or for isolation of membrane proteins. Other arteries were used for histological staining with an endothelin-B (ET(B)) receptor antibody. In arteries suspended for the measurement of isometric force, endothelin-1 produced concentration-dependent increases in tension that were significantly greater in fistula- than in sham-operated arteries without endothelium. The ET(B)-receptor-selective peptide sarafotoxin S6c produced concentration- dependent increases in tension only in fistula-operated arteries. In receptor-binding studies of membrane proteins, Scatchard analysis of saturation binding with 125I-labeled endothelin-1 (125I-endothelin-1) indicated that the total number of receptors was greater in fistula-operated arteries; affinity was threefold less in fistula- than in sham-operated arteries. Competitive displacement of 125I-endothelin-1 by endothelin-3 was significant for a two-site model in membranes prepared from sham- and fistula-operated arteries. Competitive inhibition of 125I-endothelin-1 binding by sarafotoxin S6c was significant for a one-site binding model in all arteries. Sarafotoxin S6c binding sites were elevated significantly in fistula-operated arteries. Immunohistochemical staining for the ET(B) receptor was significantly greater in both the endothelium and smooth muscle of fistula- than in sham-operated arteries. These results suggest that chronic increases in blood flow upregulate endothelin receptors, including ET(B) receptors in arterial smooth muscle.

Original languageEnglish (US)
Pages (from-to)H65-H71
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume270
Issue number1 39-1
DOIs
StatePublished - 1996

Keywords

  • arteriovenous fistula
  • endothelin-B antibody
  • remodeling
  • sarafotoxin S6c

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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