. Vasoactive effects of methylamine in isolated human blood vessels: role of semicarbazide-sensitive amine oxidase, formaldehyde, and hydrogen peroxide. Am J Physiol Heart Circ Physiol 286: H667-H676, 2004; 10.1152/ajpheart.00690. 2003.-It is hypothesized that methylamine (MA) and semicarbazidesensitive 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 mol/l) in uncontracted and norepinephrine (NE; 1 mol/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 Ϯ SE, %relax-ation: 55.4 Ϯ 3.9, n ϭ 30). The MA-induced relaxation in LIMA was repeatable, nontoxic, and age independent. Semicarbazide significantly blocked MA-induced relaxation (%inhibition: 82.5 Ϯ 4.8, n ϭ 7) and SSAO activity (%inhibition: 98.1 Ϯ 1.3, n ϭ 26) in LIMA. Formaldehyde (%relaxation: 37.3 Ϯ 18.6, n ϭ 3) and H 2O2 (%relax-ation: 55.6 Ϯ 9.0, n ϭ 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 A CURRENT HYPOTHESIS STATES that chronic methylamine (MA) exposure induces vascular injury and promotes vascular disease, including atherosclerosis, in humans via semicarbazidesensitive amine oxidase-mediated (SSAO) metabolism of MA to injurious metabolites: formaldehyde, H 2 O 2 , and ammonia (NH 3 ) (19, 50-52). Recent clinical and experimental studies support such a relationship. Altered plasma MA levels, MA excretion, and elevated plasma SSAO activity are present in human diseases associated with chronic vascular pathology [e.g., diabetes mellitus and uremia (Refs. 3,5,6,27, and 49; for reviews, see Refs. 19 and 51)]. In the case of Type I diabetes, SSAO plasma levels increase at the onset of disease (6) and plasma SSAO activity positively correlates with the amount of glycosylated hemoglobin, an indicator of the severity of complications in human diabetics (5, 43). Similarly, plasma SSAO activity is elevated within 2 wk after streptozotocin-induced diabetes in rats (22). Thus much circumstantial evidence link...
