Role of endothelin in the circulatory changes associated with small bowel strangulation obstruction in pigs: effects of the endothelin receptor antagonist bosentan.
BACKGROUND
We have previously shown that experimental strangulation obstruction leads to increased release and concentration of endothelin-1 (ET-1) in venous blood from the strangulated bowel loop. The present study focuses on the microcirculatory effects of the released ET-1 in strangulation obstruction.


METHODS
In anesthetized pigs strangulation obstruction was induced by increasing pressure in a baby pressure gasket placed around a loop of ileum until venous pressure reached 45 mm Hg. The pigs were randomly allocated into two groups. The nonselective ET(A)/ET(B) antagonist bosentan was administered intravenously (5 mg kg(-1)) to eight pigs (bosentan group) 30 min before strangulation, which was maintained for 90 min. Another eight pigs were treated in same manner except for the bosentan injection (control group).


RESULTS
The concentration of ET in arterial and intestinal venous blood increased markedly after intravenous administration of bosentan. Intravenous infusion of bosentan was followed by a reduction in systemic arterial blood pressure. Bosentan reduced vascular resistance and increased blood flow in the normal intestinal mucosa. It also reduced muscularis blood flow in the beginning of the experiment. In strangulated small bowel bosentan inhibited the increase in vascular resistance usually caused by strangulation obstruction. Muscularis blood flow in strangulated small bowel was not affected by bosentan.


CONCLUSIONS
Endothelin is involved in the normal regulation of arterial blood pressure. The increase in vascular resistance associated with strangulation obstruction is caused mainly by locally released endothelin.
Fevang
J
J
Surgical Research Laboratory, Endocrine Section, Bergen, Norway. Jonas.Fevang@kir.uib.no
Ovrebø
K
K
Myking
O
O
Grong
K
K
Svanes
K
K
D000818:Animals; D000077300:Bosentan; D003251:Constriction, Pathologic; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D005260:Female; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D007421:Intestine, Small / Q000098:blood supply*; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D013449:Sulfonamides; D000077300:Bosentan