EFFECT OF CROSS-LINKED HEMOGLOBIN TRANSFUSION ON ENDOTHELIAL-DEPENDENT DILATION IN CAT PIAL ARTERIOLES

We determined whether addition of hemoglobin to the plasma would inhib it endothelial-dependent dilation in brain where tight endothelial jun ctions limit hemoglobin extravasation. Pial arteriolar diameter was me asured by intravital microscopy through closed cranial windows in anes thetized cats either without transfusion (hematocrit = 32%) or after e xchange transfusion with an albumin or sebacyl-cross-linked human hemo globin solution (hematocrit = 18%). Dilation of small, medium, and lar ge arterioles to acetylcholine and ADP was not significantly altered b y hemoglobin transfusion. The dilatory responses were inhibited by the nitric oxide synthase inhibitor NG-nitro-L-arginine, although signifi cant dilation to 30 mu M acetylcholine persisted in small arterioles i n the control and albumin-transfused group but not in the hemoglobin-t ransfused group. The dilatory response to the nitric oxide donor 3-mor pholinosydnonimine was unaffected by albumin or hemoglobin transfusion , but the response to nitroprusside was reduced by one-third after hem oglobin transfusion. When cross-linked hemoglobin was superfused throu gh the cranial window, the acetylcholine response became inhibited at a hemoglobin concentration of 0.1 mu M and was completely blocked at 1 0 mu M. Because this concentration is substantially less than the 500 mu M hemoglobin concentration in plasma after transfusion when there w as no inhibition of the acetylcholine response, hemoglobin permeation of the blood-brain barrier was considered negligible. We conclude that exchange of red cell-based hemoglobin with plasma-based hemoglobin do es not produce a more effective sink for endothelial-derived nitric ox ide evoked by agonist receptor-mediated activation. Furthermore, decre ased hematocrit does not affect agonist-evoked endothelial-dependent d ilation.