Hydrogen peroxide as an endogenous mediator and exogenous tool in cardiovascular research: issues and considerations.

Exogenous H(2)O(2) is widely applied to cardiovascular tissues in order to elicit oxidant-dependent responses relevant to signalling and disease. Lower levels of endogenous H(2)O(2) are essential for normal physiological functioning and signalling, whereas higher levels are associated with disease. Within diseased tissues, concentrations in excess of 100 microM have been measured, though 1-15 microM appears to be the upper limit of the healthy physiological range. Analysing the kinetic constants and abundance of peroxidases suggests that they may, on occasion, encounter tissue H(2)O(2) concentrations as high as 1 mM. Extracellular application of 0.01-1 mM peroxide appears to be directly relevant to biology and broadly mimics the release of H(2)O(2) endogenously by growth factors and other effectors. However, the intracellular H(2)O(2) may only ever reach 1-15% of the applied exogenous concentration.