Presence of hemoglobin inside aortic endothelial cells after cell-free hemoglobin administration in guinea pigs

The endothelium is the production site of several potent vasoactive factors that contribute to the modulation of the vascular tone. Because hemoglobin -based oxygen carriers (HBOC) have been demonstrated to cause vasoconstrict ion and thereby increase arterial pressure by interacting with endothelium- derived factors such as nitric oxide and endothelin-1, we hypothesized that hemoglobin could penetrate into the endothelial cells. Therefore, we inves tigated the presence of hemoglobin into guinea pig aortic endothelial cells by immunohistochemical staining after exchange transfusion with a hemoglob in-based oxygen carrier. Despite the large molecular size of HBOC due to ch emical modifications designed to prevent hemoglobin subunit dissociation an d extravascular leakage, hemoglobin was detectable by immunohistochemical s taining into the endothelial cells. These findings suggest that the vascula r endothelial cells could uptake hemoglobin by endocytosis mechanisms or co uld help hemoglobin to cross the endothelial barrier toward media by transc ytosis mechanisms. These findings are very important to lead future investi gations to the mechanisms by which HBOC cause vasoconstriction.