Erythrocyte deformability is a nitric oxide-mediated factor in decreased capillary density during sepsis

1 Departments of Medical Biophysics, 2 Anaesthesia, and 3 Respirology, University of Western Ontario, London, Ontario N6A 5B8, Canada; and 4 Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis, Missouri 63104 Erythrocyte deformability has been recognized as a determinant of microvascular perfusion. Because nitric oxide (NO) is implicated in the modulation of red blood cell (RBC) deformability and NO levels increase during sepsis, we tested the hypothesis that a NO-mediated decrease in RBC deformability contributes to decreased functional capillary density (CD) in remote organs. With the use of a peritonitis model of sepsis in the rat [cecal ligation and perforation (CLP)] and aminoguanidine (AG) to prevent increases in NO, we measured CD in skeletal muscle (intravital microscopy), mean erythrocyte membrane deformability ( ; micropipette aspiration), systemic NO production [plasma nitrite/nitrate (NO x ) chemiluminescence], and NO accumulation in RBC [NO bound to hemoglobin (HbNO) detected by electron paramagnetic resonance spectroscopy]. In untreated CLP animals relative to sham, NO x increased 254% ( P