Arterial flow induces changes in saphenous vein endothelium proteins transduced by cation channels

Objectives: expression of leukocyte adhesins and proteins controlling throm bosis is likely to be an important determinant of graft patency early follo wing vein bypass. We have previously demonstrated rapid increase in endothe lial ICAM-1 and nitric oxide synthase (eNOS) concentrations in human saphen ous vein exposed to arterial flow. The aim of this study was to investigate whether ion-channel-blocking drugs could alter these flow-induced changes. Methods: human saphenous vein segments, freshly excised from patients, were placed in a validated in vitro circuit using flow conditions shown to simu late arterial or venous circulations for 90 min, in the presence ou absence of ion-channel blockers. The concentrations of ICAM-1, VCAM-1, eNOS and ti ssue factor (TF) were assessed by quantitative immunohistochemistry in vein exposed to flow and compared with that in freshly excised vein from the sa me patient. The endothelial protein concentration was calculated as the mea n area of staining as percentage of that for the control protein CD31, usin g computer-aided image analysis. Results: after arterial flow conditions the area ratio of ICAM-1 increased from 21.4+/-1.4 to 44.6+/-2.0%, of eNOS increased from 50.0+/-5.6 to 70.1+/ -5.0%, of VCAM-1 decreased from 16.6+/-3.4 to 3.6+/-1.0%, whereas TF staini ng area ratio was unchanged. Inclusion of the non-selective K+ channel bloc ker, tetraethylammonium, in the arterial perfusion solution abolished all t hese arterial flow-induced changes. Inclusion of the K-ATP(+) channel block er, glibenclamide, selectively abolished the arterial flow-induced changes in ICAM-1 and VCAM-1. Inclusion of the calcium channel blocker, nifedipine, abolished the arterial flow-induced changes in eNOS and VCAM-1 but increas ed the TF staining area ratio from 3.0+/-0.4 to 8.5+/-0.7%, p=0.01. Inclusi on of the stretch-activated cation-channel blocker, gadolinium, enhanced th e arterial flow-induced increase in eNOS, but prevented the arterial flow-i nduced increase in ICAM-1. Conclusions: perfusion of veins under arterial flow conditions with gadolin ium was associated with low endothelial concentrations of ICAM-1, VCAM-1 an d TF, but high levels of eNOS. Such a concentration of endothelial proteins may be advantageous in newly implanted vein grafts. In contrast, nifedipin e could have adverse effects by promoting increase in TF concentration.