Chronic increases in blood flow upregulate endothelin-B receptors in arterial smooth muscle.
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 (ETB) 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 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-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 ETB 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 ETB receptors in arterial smooth muscle.
Barber
D A
DA
Department of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Michener
S R
SR
Ziesmer
S C
SC
Miller
V M
VM
D000818:Animals; D001158:Arteries / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D001775:Blood Circulation / Q000502:physiology*; D004285:Dogs; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009924:Organ Culture Techniques / Q000379:methods; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism*; D012044:Regression Analysis; D013997:Time Factors; D015854:Up-Regulation; D014757:Viper Venoms / Q000378:metabolism
D019332:Endothelin-1; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6