Exogenous hyaluronidase induces release of nitric oxide from the coronary endothelium. J Thorac Cardiovasc Surg 2000 Oct;120(4):707-11
Date
09/26/2000Pubmed ID
11003752DOI
10.1067/mtc.2000.108905Scopus ID
2-s2.0-0033771174 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
OBJECTIVE: Hyaluronidase, an endogenous enzyme that hydrolyzes mucopolysaccharides, has been shown to enhance myocardial protection when added to preservation solutions. In addition, hyaluronidase infusion reduces injury to ischemic myocardium. Endothelium-derived nitric oxide is an endogenous vasodilator that prevents leukocyte adhesion to the intima and inhibits platelet adhesion and aggregation in the coronary artery. Experiments were undertaken to determine whether the protective action of hyaluronidase could be mediated by the endogenous release of nitric oxide.
METHODS: Segments of coronary artery, with and without endothelium, were placed in organ chambers (25 mL) to measure isometric force. Blood vessel segments were contracted with prostaglandin F(2)(alpha) (2 x 10(-6) mol/L) and exposed to hyaluronidase (3-15 units).
RESULTS: Hyaluronidase induced vasodilation of arteries with intact endothelium but not of arteries without endothelium (n = 6, P<.05). Endothelium-dependent vasodilation to hyaluronidase was blocked by N(G)-monomethyl-L -arginine (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 was 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 hemoglobin (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 coronary endothelium. Because nitric oxide, an endogenous vasodilator, inhibits leukocyte adhesion to the intima in addition to inhibiting platelet adhesion and aggregation, stimulated production of endothelium-derived nitric oxide by exogenous hyaluronidase could be the mechanism of the protective action of hyaluronidase infusion.
Author List
Evora PR, Pearson PJ, Chua YL, Discigil B, Schaff HVAuthor
Paul Joseph Pearson MD, PhD Chief, Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Analysis of VarianceAnimals
Arginine
Coronary Vessels
Dogs
Endothelium, Vascular
Enzyme Inhibitors
Hemoglobins
Hyaluronoglucosaminidase
Nitric Oxide
Prostaglandins F
Vasodilator Agents
omega-N-Methylarginine