Exogenous hyaluronidase induces release of nitric oxide from the coronary endothelium.
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.
Evora
P R
PR
Section of Cardiovascular Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minn., USA. prbevora@keynet.com.br
Pearson
P J
PJ
Chua
Y L
YL
Discigil
B
B
Schaff
H V
HV
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D011460:Prostaglandins F / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006454:Hemoglobins; D011460:Prostaglandins F; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D006821:Hyaluronoglucosaminidase