Sulodexide Promotes Venous Contraction in Rat Inferior Vena Cava

Abstract

Sulodexide (SDX) is a highly purified glycosaminoglycan composed of fast-moving heparin (80%) and dermatan sulfate (20%). SDX has both antithrombotic and profibrinolytic properties with reported benefits in chronic venous disease and other thrombotic and atherosclerotic vascular disorders. However, the effects of SDX on the vein wall structure and function are unclear. We have previously shown that matrix metalloproteinases 2 and 9 cause venous relaxation, and other studies have suggested that SDX may inhibit matrix metalloproteinase 9. The purpose of this study was to test whether SDX affects venous function and whether its venous effects are different from those in the arteries. Male rat inferior vena cava (IVC), abdominal aorta, and mesenteric artery were harvested and 3-mm circular segments were equilibrated under 0.5g, 2g, and 1g basal tension, respectively, in a tissue bath containing Krebs solution bubbled with 95% O2 5% CO2 at 37°C, and the changes in isometric contraction were recorded. Vessel segments were precontracted with the α-adrenergic receptor agonist phenylephrine (PHE, 3 × 10−7 M), and the changes in the vessel response to SDX (0.001-1 mg/mL) were measured. The % venous/arterial contraction or relaxation was calculated, and the data were presented as means ± standard error of the mean and analyzed with t-test, with P < .05 significant. In the IVC, aorta, and mesenteric artery, PHE (3 × 10−7 M) caused submaximal contraction that remained steady for at least 1 hour. In PHE-precontracted IVC, SDX caused concentration-dependent increases in contraction that reached a maximum at 1 mg/mL (SDX 62.8 ± 3.9 vs control 0.0; P < .01). In contrast, in PHE-precontracted aorta and mesenteric artery, SDX caused concentration-dependent relaxation compared with control (maximum 45.4 ± 6.0 vs 6.7 ± 6.6; 39.3 ± 6.2 vs 0.0, respectively; P < .05). SDX potentiates contraction in veins while causing relaxation in arteries. The mechanisms may involve differential effects of SDX on different matrix metalloproteinase subtypes, protease-activated receptors, and integrins in the veins vs arteries and need to be further examined. The results may have clinical implications as SDX may be helpful as a venotonic agent for chronic venous disease while promoting arterial dilation and decreasing arterial pressure.