Formation of formaldehyde from adrenaline in vivo; a potential risk factor for stress-related angiopathy

Cardiovascular and cerebrovascular disorders are well known to be associated with stress related behaviors. Stress enhances excretion of adrenaline, which is deaminated by monoamine oxidase and methylamine is formed. This product can be further deaminated by semicarbazide-sensitive amine oxidase (SSAO) and converted to toxic formaldehyde, hydrogen peroxide and ammonia. SSAO is located in the cardiovascular smooth muscles and circulated in the blood. We investigated whether formaldehyde can be derived from adrenaline in vivo. Methylamine was confirmed to be a product of adrenaline catalyzed by type A monoamine oxidase (MAO-A). Irreversible and long-lasting radioactive residual activity was detected in different tissues following administration of 1-[N-methyl-3H]-adrenaline. Such irreversible linkage could be blocked by selective MAO-A or SSAO inhibitors. Endothelial cells are quite sensitive to formaldehyde and relatively resistant to hydrogen peroxide. It is possible that stimulation of adrenaline excretion by chronic stress could increase the levels of circulatory formaldehyde. Such chronic "formaldehyde" stress may be involved in the initiation of endothelial injury and subsequently angiopathy.