Question: 

The monoamine oxidases (MAOs) are mitochondrial enzymes which through an oxidative step degrade biogenic amines. A byproduct of MAO activity is reactive oxygen species (ROS) and thus MAOs may potentially contribute to vascular dysfunction. We hypothesized that MAO inhibition improves endothelial NO-dependent vasodilation in vascular disease conditions associated with oxidative stress.

Methodology: 

To study this, mice were treated with lipopolysaccharide (LPS, 8mg/kg, single injection) or angiotensin II (AngII, 1mg/kg/d by osmotic minipumps for 7 days). Subsequently, the effect of MAO inhibition on endothelium-dependent relaxation (EDR) in response to acetylcholine was studied in isolated phenylephrine-preconstricted aortic segments in the presence of diclofenac (10mmol/L).

Results: 

AngII induced pronounced attenuation of EDR. If experiments were done in the presence of the MAO-A inhibitor clorgiline (10mmol/L), EDR in control segments was unaffected. In contrast, the compound restored normal EDR in segments of mice receiving AngII. Similarly, after LPS treatment, endothelial dysfunction was apparent and also in this situation normal EDR was restored by clorgiline. The compound also attenuated the agonist-induced constriction in response to phenylephrine but also to the thromboxan analog U46619, and this effect was endothelium-independent.

Conclusions: 

The MAO-A inhibitor Clorgiline might be useful in restoring EDR in situations of increased vascular oxidative stress and endothelial dysfunction.