Monoamine oxidase--a inhibition reverses endothelial dysfunction in hypertensive rat aortic rings.

Aim: Monoamine oxidases (MAOs) are mitochondrial enzymes, with 2 isoforms, A and B that convert biogenic amines to their corresponding aldehydes via a reaction that produces hydrogen peroxide. Since MAO-A is the predominant form at vascular level we hypothesized that MAO-A-dependent H2O2 production may contribute to the development of endothelial dysfunction and, MAOs inhibition could improve the vascular function, respectively.

Material And Methods: To this aim aortic rings were isolated from female adult spontaneously hypertensive rats (SHR) and their corresponding (Wistar-Kyoto) controls. The effect of MAO-A inhibitor, clorgyline (10 micromol/l) on endothelium-dependent relaxation (EDR) in response to acetylcholine and endothelium-independent relaxation in response to sodium nitroprusside, was studied in isolated phenylephrine-preconstricted aortic segments in the presence of indometacine (10 micromol/l).

Results: In hypertensive group EDR was significantly decreased - maximal relaxation (% of KCI, mean +/- SD) being 37 +/- 3.5 in SHR vs. 3.7 +/- 1.8 in controls. If experiments were done in the presence of clorgyline, EDR in control segments was unaffected. However, the compound restored normal EDR in aortic segments from hypertensive rats (maximal relaxation % of KCI, 13.7 +/- 2.3).

Conclusions: Inhibition of the MAO-A isoform might be useful in restoring endothelium-dependent relaxation in this experimental model of hypertension in rat.