Abstract
Hemoglobin-mediated cytotoxicity and constriction of blood vessels represent serious obstacles in the development of acellular hemoglobin derivatives to be used as artificial oxygen carriers. The principal property of hemoglobin that may potentially lead to vasoconstriction in vivo is its interaction with the endothelium-derived relaxing factor (EDRF), a local regulator of blood pressure that has been identified as nitric oxide (NO). EDRF-NO, which is synthesized in endothelial cells from L-arginine by NO synthase, mediates vascular smooth muscle relaxation by activation of the heme-dependent enzyme guanylate cyclase. It appears that cell-free hemoglobin injected into the vascular circulation may rapidly extra-vasate to the surrounding tissues, where it binds NO more avidly than oxygen, blocking the vasorelaxant properties of EDRF. In addition, since NO mediates important regulatory processes in the cell, the inactivation of NO functions by the use of hemoglobin preparations may significantly alter the hemostasis of vascular endothelium and other tissues.
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Motterlini, R. (1996). Interaction of Hemoglobin with Nitric Oxide and Carbon Monoxide: Physiological Implications. In: Winslow, R.M., Vandegriff, K.D., Intaglietta, M. (eds) Blood Substitutes. Birkhäuser Boston. https://doi.org/10.1007/978-1-4612-4114-0_5
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DOI: https://doi.org/10.1007/978-1-4612-4114-0_5
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