Desmopressin induces adhesion of normal human erythrocytes to the endothelial surface of a perfused microvascular preparation

Abstract

The interaction of red blood cells (RBCs) with vascular endothelium under flow conditions was investigated using the perfused rat mesocecum. Under videomicroscopy, normal human erythrocytes were found to adhere to the venular endothelium of desmopressin-treated microvasculature. Transmission electron microscopy showed that the erythrocytes were attached to the endothelial cells at discrete electron-dense sites. Compared with control preparations in which the microvasculature was perfused with Ringer's-albumin solution alone, more than a 10-fold increase in radioactivity was retained in the desmopressin-treated microvasculature when technetium (99mTc)-labeled erythrocytes were infused into the vasculature. This erythrocyte adherence was accompanied by a higher increment in vascular resistance during the passage of RBCs through the microcirculation, and by a delay in the recovery toward baseline. The erythrocyte adherence in desmopressin-treated microvasculature was completely abolished with antibodies to von Willebrand factor (vWF). Desmopressin infusion in rats resulted in elevated vWF antigen levels and the appearance of extra-large molecular weight forms of vWF in plasma. These findings suggest that normal erythrocytes adhere to desmopressin-conditioned microvascular endothelium and that endothelial cell-derived vWF is involved in the erythrocyte-endothelium interaction.

Desmopressin (DDAVP) in the treatment of bleeding disorders: the first twenty years

“…Other putative mechanisms or mediators have been proposed to explain the haemostatic efficacy of desmopressin. For instance, the compound induces the adhesion of erythrocytes to the endothelium [30] and decreases the endothelial production of 13‐hydroxyoctadecadienoic acid (HODE), a derivative of linoleic acid that powerfully inhibits platelet adhesion to the vessel wall [31]. The role of these mechanisms is uncertain and the search for additional or alternative mechanisms of action has been unfruitful so far.…”

Glycoprotein Ib Can Mediate Endothelial Cell Attachment to a von Willebrand Factor Substratum

“…These observations raise the interesting pos sibility that vWF, along with other matrix constituents like fibronectin and collagen, might play a role in EC attachment to subendothelium (4,5). In addition, there is evidence that vWF may bind to the apical surface of endothelial cells and mediate the adhesion of red blood cells to the blood vessel wall in sickle cell disease (7,8).…”

Platelet-independent adhesion of calcium-loaded erythrocytes to von Willebrand factor

“…An example of this experiment can be seen in S1 Video . Previously, the release of ULVWF multimers from ECs was shown to cause adhesion of normal erythrocytes to the venular endothelium in an ex vivo rat mesocecum model [ 12 ]. Thrombin and histamine may induce increased release of endothelial ULVWF multimers during episodes of vascular injury, inflammation, and infection [ 21 , 22 ].…”

“…In addition to SS erythrocytes, also calcium-loaded erythrocytes can adhere to ECs [ 7 ]. Furthermore, in the ex vivo rat mesocecum model perfused with desmopressin, it was shown that ULVWF released from ECs also promoted the adhesion of normal erythrocytes to the venular endothelium [ 12 ]. Based on these previous findings, we investigated whether calcium loading of erythrocytes could enhance the binding of erythrocytes to ECs via ULVWF multimers.…”