Day-night variations in blood levels of nitric oxide, T-TFPI, and E-selectin

Circadian (8/24 hours) variations in serum nitric oxide (NO). total tissue factor pathway inhibitor (T-TFPI), and E-selectin levels were studied in he althy adults and in subjects with type II diabetes. We postulated a possibi lity a functional relationship between them because vascular endothelium is the primary site of their synthesis and functions. NO is released by the a ction of eNO synthase isoform and modulates physiologic responses (e.g., va scular dilation, relaxation, increasing blood flow, inhibition of platelet and white blood cell adhesion); T-TFPI, a coagulation inhibitor, is also re leased from endothelial cells, and is bound to plasma lipoproteins and to g lycosaminoglycans; E-selectin is expressed on endothelial cells after activ ation by inflammatory cytokines (interleukin-1 beta and tumor necrosis fact or-alpha) and elevated levels have been reported in a variety of pathologic conditions, including diabetes, We found that obese diabetic subjects had greater mean concentrations of NO and E-selectin than healthy men, 39.25 ve rsus 12.71 muM and 81.51 versus 26.03 ng/mL, respectively. The T-TFPI level s were essentially similar in both groups of men. 47.10 versus 48.76 ng/mL. We observed that the time of peak concentrations of T-TFPI and E-selectin was similar to the timing of NO trough levels, suggesting a possible functi onal relationship. It may be hypothesized. therefore, that the higher conce ntrations of NO, unbalanced by increases in T-TFPI and E-selectin, may resu lt in increased vascular wall uptake of lipoproteins in diabetic subjects, who are at greater risk than healthy men for developing diffuse atheroscler osis.