Chronic increases in blood flow upregulates endothelin-b receptors
in arterial smooth muscle.
Barber, Dustan A., Sandra R. Michener, Steven C. Ziesmer, and Virginia
M. Miller.
Departments of Surgery, Physiology and Biophysics, Mayo Clinic and
Foundation, Rochester, MN 55905
APStracts 2:0318H, 1995.
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 hind limb of dogs;
contralateral blood vessels were sham operated. Sham- and fistula
-operated arteries were removed six weeks 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 receptor (ETB) antibody.
In arteries suspended for the measurement of isometric force,
endothelin-1 produced concentration-dependent increases in tension
that were significantly greater in fistula- compared to sham-operated
arteries without endothelium. The ETB-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-endothelin-1 indicated that the total number of receptors was
greater in fistula-operated arteries; affinity was three-fold less in
fistula- compared to 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 ETB receptor
was significantly greater in both the endothelium and smooth muscle
of fistula- compared to sham-operated. These results suggest that
chronic increases in blood flow upregulate endothelin receptors
including ETB receptors in arterial smooth muscle.
Received 8 May 1995; accepted in final form 29 June 1995.
APS Manuscript Number H430-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 August 1995.