Changes in plasma levels of cyclic nucleotides during low-density lipoprotein apheresis

The negative charges of dextran sulfate (DS) used for low-density lipoprotein (LDL) apheresis activate the intrinsic coagulation pathway, accompanied by the production of bradykinin. This study was undertaken to see whether cyclic nucleotide plasma levels are affected by DS LDL apheresis. Previously, we showed the rise in plasma levels of prostaglandins and nitric oxide derivatives accompanied by the rise in bradykinin levels. The physiologic effects of prostaglandins and nitric oxide become manifest through the intracellular signal of cyclic nucleotides. The plasma levels of the cyclic nucleotides (cyclic adenosine monophosphate [cAMP] and cyclic guanosine monophosphate [cGMP]) were examined when either of 2 anticoagulants, heparin or nafamostat mesilate (NM), was used during DS LDL apheresis. The plasma levels of cAMP during LDL apheresis using heparin were 9.2 +/- 0.3 (mean +/- SE) 12.4 +/- 0.6, 12.0 +/- 0.5, and 12.1 +/- 0.3 pmol/ml, respectively, at the 0, 1,000, 2,000, and 3,000 ml stages. The rise in cAMP levels was suppressed during apheresis using NM. There were no significant increases in cGMP during apheresis with heparin or with NM. There were significant negative correlations between changes in cAMP and those in the blood pressure. These findings suggest that bradykinin generated during apheresis exerts some physiologic effects via activation of the adenylate cyclase dependent pathway.