Endothelin-a receptor antagonist treatment improves the periosteal microcirculation after hindlimb ischemia and reperfusion in the rat.
OBJECTIVE
To examine the microcirculatory changes in the rat tibial periosteum after hindlimb ischemia and reperfusion and to evaluate the effects of endothelin-A (ET-A) receptor antagonist therapy in this condition. The healing and functioning of vascularized bone autografts depend mainly on the patency of the microcirculation, and the activation of ET-A receptors may be an important component of the tissue response that occurs during ischemia-reoxygenation injuries.


METHODS
Wistar rats were subjected to 1 hour of hindlimb ischemia and 3 hours of reperfusion. The periosteal microcirculation was visualized by intravital fluorescence microscopy. The leukocyte rolling and adherence in the postcapillary venules and the functional capillary density of the periosteum were determined. Two separate groups were treated with the selective ET-A receptor antagonist BQ 610 or the novel ET-A receptor antagonist ETR-p1/fl peptide at the onset of reperfusion.


RESULTS
Reperfusion was accompanied by a significant decrease in functional capillary density and by an increase in the primary and secondary leukocyte-endothelial cell interactions. ET-A receptor inhibition reduced the leukocyte rolling and firm adherence and attenuated the decrease in functional capillary density in both treated groups.


CONCLUSIONS
ET-1 plays a major role in microvascular dysfunction in the periosteum during reperfusion. The ET-1-ET-A receptor system might be an important target for tissue salvage therapy in transplantation surgery.
Wolfárd
Antal
A
Department of Surgery, University of Szeged, Szent-Györgyi Albert Medical and Pharmeceutical Center, Szeged, Hungary.
Császár
József
J
Gera
László
L
Petri
András
A
Simonka
János Aurél
JA
Balogh
Adáa
A
Boros
Mihály
M
D000818:Animals; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000473:pathology; D006614:Hindlimb; D036341:Intercellular Signaling Peptides and Proteins; D036904:Leukocyte Rolling; D008297:Male; D051379:Mice; D008833:Microcirculation / Q000187:drug effects / Q000473:pathology; D018715:Microscopy, Video; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010521:Periosteum / Q000098:blood supply*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy*; D013977:Tibia
C109027:ETR-p1-f1 antisense peptide; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010455:Peptides; C087220:BQ 610