Exogenous hyaluronidase induces release of nitric oxide from the coronary endothelium

Objective: Hyaluronidase, an endogenous enzyme that hydrolyzes mucopolysacc harides, has been shown to enhance myocardial protection when added to pres ervation solutions. In addition, hyaluronidase infusion reduces injury to i schemic myocardium. Endothelium-derived nitric oxide is an endogenous vasod ilator that prevents leukocyte adhesion to the intima and inhibits platelet adhesion and aggregation in the coronary artery. Experiments were undertak en to determine whether the protective action of hyaluronidase could be med iated by the endogenous release of nitric oxide. Methods: Segments of coronary artery, with and without endothelium, were pl aced in organ chambers (25 mL) to measure isometric force. Blood vessel seg ments were contracted with prostaglandin F-2 alpha (2 x 10(-6) mol/L) and e xposed to hyaluronidase (3-15 units). Results: Hyaluronidase induced vasodilation of arteries with intact endothe lium but not of arteries without endothelium (n = 6, P <.05). Endothelium-d ependent vasodilation to hyaluronidase was blocked by N-G-monomethyl-L-argi nine (10(-5) mol/L), an inhibitor of nitric oxide synthesis from L-arginine (n = 6, P <.05). Inhibition of vasodilation by N-G-monomethyl-L-arginine w as reversed by L-arginine (10(-4) mol/L) but not D-arginine (10(-4) mol/L; n = 6, each group). Vasodilation to hyaluronidase also was inhibited by hem oglobin (2 x 10(-6) mol/L), a scavenger of the nitric oxide radical (n = 6, P <.05). Conclusions: Hyaluronidase induces the release of nitric oxide from the cor onary endothelium. Because nitric oxide, an endogenous vasodilator, inhibit s leukocyte adhesion to the intima in addition to inhibiting platelet adhes ion and aggregation, stimulated production of endothelium-derived nitric ox ide by exogenous hyaluronidase could be the mechanism of the protective act ion of hyaluronidase infusion.