Sulodexide Improves Contraction and Decreases Matrix Metalloproteinase-2 and -9 in Veins Under Prolonged Stretch

Abstract: High pressure in the lower-limb veins is often associated with chronic venous insufficiency and varicose veins (VVs), making it important to search for the mechanisms and agents that control venous function. We have shown that protracted increases in venous stretch/wall tension reduce vein contraction and augment matrix metalloproteinase (MMP)-2 and -9. Also, MMP-2 and MMP-9 promote venodilation, a hallmark of VVs. Sulodexide (SDX) is a blend of glycosaminoglycans with efficient profibrinolysis and antithrombosis activities, but its actions on vein function and the mechanisms involved are unclear. We tested the hypothesis that SDX enhances venous contractile response by decreasing MMP expression/activity in veins subjected to protracted stretch. Rat inferior vena cava (IVC) rings were treated with SDX (0.001–1 mg/mL) or vehicle, equilibrated under control 0.5-g resting tension or protracted 2-g stretch for 18 hours, and the contractile response to 96-mM KCl and phenylephrine (Phe) in SDX-treated and nontreated veins was recorded. In IVC rings under control 0.5-g resting tension, SDX caused dose-dependent contraction, 96-mM KCl caused marked contraction (176-mg/mg tissue), and Phe caused dose-dependent contraction with a maximum (56-mg/mg tissue) at 10−5 M. In IVC subjected to protracted 2-g stretch, 96-mM KCl-induced contraction was reduced to 112 mg/mg and maximal Phe-induced contraction was decreased to 23 mg/mg. In IVC subjected to protracted 2-g stretch pl...
Source: Journal of Cardiovascular Pharmacology - Category: Cardiology Tags: Original Article Source Type: research