Effect of endothelin-1 infusion on the development of intimal hyperplasia after balloon catheter injury.
Previous studies have shown endothelin-1 (ET-1) to be mitogenic for smooth-muscle cells. We explored in vivo the ability of high ET-1 levels to worsen angioplasty restenosis. Left carotid artery balloon endothelial denudation was performed on 14 rats. ET-1 was delivered via osmotic pump at a rate of 5 pmol/kg/min. Intimal development and plasma ET-1 levels were assessed at 2 weeks. Blood pressure and heart rate were measured throughout the study. For analysis, the animals were divided into three groups based on ET-1 levels at harvest: control, 4.3 +/- 0.5 pmol/ml (n = 6); low ET-1, 5.2 +/- 0.9 pmol/ml (n = 4); and high ET-1, 23.1 +/- 5.9 pmol/ml (n = 4). Although ET-1 infusion caused blood pressure elevation in both ET-1 groups, this was more marked and prolonged in the group with a high ET-1 level at study conclusion. Evaluation of the intimal:medial area ratio showed a marked increase in intimal thickness in the high ET-1 group versus control (1.13 +/- 0.23 versus 0.35 +/- 0.11; p < 0.05). We conclude that ET-1 infusion in responsive animals can cause worsening of the intimal hyperplastic response after mechanical injury. Further study is required to elucidate whether this is entirely caused by a direct effect of ET-1 on smooth-muscle cell mitogenesis or is also by the hemodynamic effects of ET-1-induced hypertension, or an effect of another mediator released in response to the ET-1 (e.g., angiotensin II).
Trachtenberg
J D
JD
Department of Surgery, Washington University School of Medicine, Wohl Clinic, St. Louis, Missouri.
Sun
S
S
Choi
E T
ET
Callow
A D
AD
Ryan
U S
US
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D002404:Catheterization / Q000009:adverse effects*; D016232:Endothelins / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006965:Hyperplasia / Q000139:chemically induced; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects
D016232:Endothelins