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SUMMARY: Nitric oxide (NO) is a powerful vascular and neural regulator. One of the breakdown products of nitric oxide is nitrite which converts to nitrous acid, a reagent routinely used for the degradation of heparin and heparan sulfate. We have recently shown that nitric oxide gas degrades heparin and heparan sulfate through a nitrous acid mechanism (Vilar et al, 1997, Biochemical Journal, 324,473-479). The purpose of the present 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 releases a steady-state level of nitrite of over 200 ~tM. This level substantially degrades heparin and heparan sulfate at a pH of up to 5.0. This reaction may be important in breakdown of the glycosaminoglycan components of the extracellular matrix during normal and pathological conditions.

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