THE NITRIC-OXIDE DONOR S-NITROSO-N-ACETYL-D,L-PENICILLAMINE DEGRADES HEPARAN-SULFATE AND HEPARIN

Nitric oxide (NO) is a powerful vascular and neural regulator. One of the breakdown products of nitric oxide is nitrite which converts to ni trous acid, a reagent routinely used for the degradation of heparin an d heparan sulfate. We have recently shown that nitric oxide gas degrad es heparin and heparan sulfate through a nitrous acid mechanism (Vilar et al, 1997, Biochemical Journal, 324, 473-479). The purpose of the p resent study is to confirm these findings using the nitric oxide donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) under conditions that are close to those found in vivo. The results show that 2 mM SNAP release s a steady-state level of nitrite of over 200 mu M. This level substan tially degrades heparin and heparan sulfate at a pH of up to 5.0. This reaction may be important in breakdown of the glycosaminoglycan compo nents of the extracellular matrix during normal and pathological condi tions.