TY - JOUR
T1 - Exogenous hyaluronidase induces release of nitric oxide from the coronary endothelium
AU - Evora, Paulo R.B.
AU - Pearson, Paul J.
AU - Chua, Yeow Leng
AU - Discigil, Berent
AU - Schaff, Hartzell V.
N1 - Funding Information:
Supported in part by The FAPESP-Fundacao de Amparo a Pesquisa do Estado de São Paulo and the Mayo Foundation.
PY - 2000
Y1 - 2000
N2 - 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(2α) (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.
AB - 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(2α) (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.
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U2 - 10.1067/mtc.2000.108905
DO - 10.1067/mtc.2000.108905
M3 - Article
C2 - 11003752
AN - SCOPUS:0033771174
SN - 0022-5223
VL - 120
SP - 707
EP - 711
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 4
ER -