Endothelin-A Receptor Antagonist Treatment Improves the Periosteal Microcirculation After Hindlimb Ischemia and Reperfusion in the Rat

ABSTRACT Objectives: 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 leukocyteendothelial 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.