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Vasoactive effects of methylamine in isolated human blood vessels: role of semicarbazide-sensitive amine oxidase, formaldehyde, and hydrogen peroxide

¹Division of Cardiology, Department of Medicine, University of Louisville, Louisville, Kentucky 40202; ²Department of Biology, University of Wisconsin, and ³Department of Cardiothoracic Surgery, Luther Hospital/Midelfort Clinic, Eau Claire, Wisconsin 54702; and ⁴Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555-0609

Submitted 18 July 2003 ; accepted in final form 14 October 2003

It is hypothesized that methylamine (MA) and semicarbazide-sensitive amine oxidase (SSAO) activity are involved in the cardiovascular complications in human diabetics. To test this, we 1) determined the acute vasoactive effects of MA (1–1,000 µmol/l) in uncontracted and norepinephrine (NE; 1 µmol/l)-precontracted human blood vessels used for coronary artery bypass grafts [left internal mammary artery (LIMA), radial artery (RA), and right saphenous vein (RSV)]; 2) tested whether MA effects in LIMA and RSV were dependent on SSAO activity using the SSAO inhibitor semicarbazide (1 mmol/l, 15 min); 3) determined the effects of MA metabolites formaldehyde and hydrogen peroxide in LIMA and RSV; 4) tested whether the MA response was nitric oxide, prostaglandin, or hyperpolarization dependent; 5) measured the LIMA and RSV cGMP levels after MA exposure; and 6) quantified SSAO activity in LIMA, RA, and RSV. In NE-precontracted vessels, MA stimulated a biphasic response in RA and RSV (rapid contraction followed by prolonged relaxation) and dominant relaxation in LIMA (mean ± SE, %relaxation: 55.4 ± 3.9, n = 30). The MA-induced relaxation in LIMA was repeatable, nontoxic, and age independent. Semicarbazide significantly blocked MA-induced relaxation (%inhibition: 82.5 ± 4.8, n = 7) and SSAO activity (%inhibition: 98.1 ± 1.3, n = 26) in LIMA. Formaldehyde (%relaxation: 37.3 ± 18.6, n = 3) and H₂O₂ (%relaxation: 55.6 ± 9.0, n = 9) at 1 mmol/l relaxed NE-precontracted LIMA comparable with MA. MA-induced relaxation in LIMA was nitric oxide, prostaglandin, and possibly cGMP independent and blocked by hyperpolarization. We conclude that vascular SSAO activity may convert endogenous amines, like MA, to vasoactive metabolites.

amine metabolism; coronary artery bypass grafts; diabetes; H₂O₂

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