OXYHEMOGLOBIN-INDUCED CYTOTOXICITY AND ARACHIDONIC-ACID RELEASE IN CULTURED BOVINE ENDOTHELIAL-CELLS

Background and Purpose: An impairment of endothelial ftinction is asso ciated with vasospasm after subarachnoid hemorrhage. Oxyhemoglobin is considered to be a critical trigger in the pathogenesis of vasospasm. The present studies examined the direct effects of oxyhemoglobin on cu ltured endothelial cells from bovine carotid artery. Methods. Confluen t endothelial cells were treated with oxyhemoglobin, and the following were studied: 1) cell morphology, 2) cell density, and 3) the release of radiolabel from [H-3]arachidonic acid-treated cells. Results: Endo thelial cells exposed to oxyhemoglobin exhibited detachment vacuoles, and cell density was significantly decreased in time- and dose-depende nt manners. Superoxide dismutase, a free radical scavenger, provided p artial protection against the cytotoxic effects of oxyhemoglobin. The release of radiolabel from [H-3]arachidonic acid-treated cells was inc reased by oxyhemoglobin in time- and dose-dependent manners. Treatment with an inhibitor of phospholipase A2 or a calcium chelator inhibited the effects of oxyhemoglobin on arachidonic acid release and cellular viability. Conclusions. Oxyhemoglobin exerts a direct cytotoxic effec t on cultured endothelial cells, and this effect is associated with in creased release from [H-3]arachidonic acid-labeled cells. Phospholipas e A2 and free radicals appear to participate in the pathogenesis of en dothelial cell damage. Oxyhemoglobin-induced compromise of endothelial cells may contribute to cerebrovascular pathology.