Chronic venous disease (CVD) is a proqgressive and underestimated condition related to a vicious circle established by venous reflux and endothelial inflammation, leading to vein dilation and histology distortion, including loss of media tone. Sulodexide (SDX) is a drug restoring the glycocalyx that demonstrated endothelial protection and permeability regulation, together with anti-thrombotic and anti-inflammatory roles. In the lab it also exhibited vein contractility function. The aim of the present study was to show the possible role of endothelium and nitric oxide pathway on SDX's veno-contractile effect on human saphenous veins. The remnants of great saphenous vein (GSV) segments (n = 14) were harvested during coronary artery bypass graft surgery. They were dissected as endothelium-intact (n = 8) and denuded rings (n = 6). First, a viability test was carried out in bath with Krebs-Henseleit solution to investigate a control and basal tension value. After this, cumulative doses of SDX were applied to rings and contraction values were studied in endothelium-intact phenylephrine (PheE, 6 × 10-7 M) pre-contracted vein rings. Finally, endothelium-intact PheE pre-contacted vein rings were treated by nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 10-4 M) for 10 min. Contraction protocol was applied, and contraction values were measured in cumulative doses of SDX. The same protocol was applied to endothelium-denuded vein rings to investigate the effect of SDX. Saphenous vein rings showed an increase in contraction to cumulative doses of SDX. In endothel-intact rings, KCL-induced contraction from 92.6% ± 0.3 to 112.9% ± 0.4 with cumulative SDX doses. However, SDX did not show any veno-contractile effect on endothel-denuded rings. In denuded rings contraction responses measured from 94.9% ± 0.3 to 85.2% ± 0.3 with increasing doses of SDX, indicating no significant change. Nitric oxide synthase inhibitor (L-NAME) prohibited the contraction response of the sulodexide in all dosages, indicating that the contractile function of SDX was mediated by endothelial derived nitric oxide. Results of endothel-intact and denuded rings with L-NAME showed a similar incline with denuded rings with SDX only. The results confirmed SDX's veno-contractile effect in human samples, by means of nitric oxide synthase pathways involvement.
Sulodexide Develops Contraction in Human Saphenous Vein via Endothelium-Dependent Nitric Oxide Pathway
Sergio Gianesini;
2023
Abstract
Chronic venous disease (CVD) is a proqgressive and underestimated condition related to a vicious circle established by venous reflux and endothelial inflammation, leading to vein dilation and histology distortion, including loss of media tone. Sulodexide (SDX) is a drug restoring the glycocalyx that demonstrated endothelial protection and permeability regulation, together with anti-thrombotic and anti-inflammatory roles. In the lab it also exhibited vein contractility function. The aim of the present study was to show the possible role of endothelium and nitric oxide pathway on SDX's veno-contractile effect on human saphenous veins. The remnants of great saphenous vein (GSV) segments (n = 14) were harvested during coronary artery bypass graft surgery. They were dissected as endothelium-intact (n = 8) and denuded rings (n = 6). First, a viability test was carried out in bath with Krebs-Henseleit solution to investigate a control and basal tension value. After this, cumulative doses of SDX were applied to rings and contraction values were studied in endothelium-intact phenylephrine (PheE, 6 × 10-7 M) pre-contracted vein rings. Finally, endothelium-intact PheE pre-contacted vein rings were treated by nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 10-4 M) for 10 min. Contraction protocol was applied, and contraction values were measured in cumulative doses of SDX. The same protocol was applied to endothelium-denuded vein rings to investigate the effect of SDX. Saphenous vein rings showed an increase in contraction to cumulative doses of SDX. In endothel-intact rings, KCL-induced contraction from 92.6% ± 0.3 to 112.9% ± 0.4 with cumulative SDX doses. However, SDX did not show any veno-contractile effect on endothel-denuded rings. In denuded rings contraction responses measured from 94.9% ± 0.3 to 85.2% ± 0.3 with increasing doses of SDX, indicating no significant change. Nitric oxide synthase inhibitor (L-NAME) prohibited the contraction response of the sulodexide in all dosages, indicating that the contractile function of SDX was mediated by endothelial derived nitric oxide. Results of endothel-intact and denuded rings with L-NAME showed a similar incline with denuded rings with SDX only. The results confirmed SDX's veno-contractile effect in human samples, by means of nitric oxide synthase pathways involvement.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
